Hier finden Sie die aktuellsten Publikationen aus dem Gebiet der Nuklearmedizin in Österreich. Zusätzlich sind die Publikationen aus den Teilbereichen der PET, SPECT sowie nuklearmedizinischen Therapien unserer Kollegen in Österreich gesondert hervorgehoben.
Rezente Publikationen in Österreich
Fibroblast Activation Protein-Directed Imaging Outperforms F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial
Kessler L, Schwaning F, Metzenmacher M, Pabst K, Siveke J, Trajkovic-Arsic M, Schaarschmidt B, Wiesweg M, Aigner C, Plönes T, Darwiche K, Bölükbas S, Stuschke M, Umutlu L, Nader M, Theegarten D, Hamacher R, Eberhardt WEE, Schuler M, Herrmann K, Fendler WP and Hautzel H
Fibroblast Activation Protein-Directed Imaging Outperforms F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial
Kessler L, Schwaning F, Metzenmacher M, Pabst K, Siveke J, Trajkovic-Arsic M, Schaarschmidt B, Wiesweg M, Aigner C, Plönes T, Darwiche K, Bölükbas S, Stuschke M, Umutlu L, Nader M, Theegarten D, Hamacher R, Eberhardt WEE, Schuler M, Herrmann K, Fendler WP and Hautzel H
The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a Ga-FAPI46 PET observational trial (NCT04571086). Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the Ga-FAPI46 PET observational trial. All patients underwent Ga-FAPI46 PET/CT, contrast-enhanced CT, and F-FDG PET/CT. The primary study endpoint was the association of Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with F-FDG PET/CT. Datasets were interpreted by 2 masked readers. The primary endpoint was met, and the association between Ga-FAPI46 SUV or SUV and histopathologic FAP expression was significant (SUV: = 0.49, = 0.037; SUV: = 0.51, = 0.030).Ga-FAPI46 and F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher Ga-FAPI46 than F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). We confirm an association of Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for Ga-FAPI46 versus F-FDG.
Sedation-free pediatric [F]FDG imaging on totalbody PET/CT with the assistance of artificial intelligence
Zhou X, Xue S, Li L, Seifert R, Dong S, Chen R, Huang G, Rominger A, Liu J and Shi K
Sedation-free pediatric [F]FDG imaging on totalbody PET/CT with the assistance of artificial intelligence
Zhou X, Xue S, Li L, Seifert R, Dong S, Chen R, Huang G, Rominger A, Liu J and Shi K
While sedation is routinely used in pediatric PET examinations to preserve diagnostic quality, it may result in side effects and may affect the radiotracer's biodistribution. This study aims to investigate the feasibility of sedation-free pediatric PET imaging using ultra-fast total-body (TB) PET scanners and deep learning (DL)-based attenuation and scatter correction (ASC).
An in vivo high-resolution human brain atlas of synaptic density
Johansen A, Beliveau V, Colliander E, Raval NR, Dam VH, Gillings N, Aznar S, Svarer C, Plavén-Sigray P and Knudsen GM
An in vivo high-resolution human brain atlas of synaptic density
Johansen A, Beliveau V, Colliander E, Raval NR, Dam VH, Gillings N, Aznar S, Svarer C, Plavén-Sigray P and Knudsen GM
Synapses are fundamental to the function of the central nervous system and are implicated in a number of brain disorders. Despite their pivotal role, a comprehensive imaging resource detailing the distribution of synapses in the human brain has been lacking until now. Here, we employ high-resolution PET neuroimaging in healthy humans (17F/16M) to create a 3D atlas of the synaptic marker Synaptic Vesicle glycoprotein 2A (SV2A). Calibration to absolute density values (pmol/mL) was achieved by leveraging postmortem human brain autoradiography data. The atlas unveils distinctive cortical and subcortical gradients of synapse density that reflect functional topography and hierarchical order from core sensory to higher-order integrative areas - a distribution that diverges from SV2A mRNA patterns. Furthermore, we find a positive association between IQ and SV2A density in several higher-order cortical areas. This new resource will help advance our understanding of brain physiology and the pathogenesis of brain disorders, serving as a pivotal tool for future neuroscience research. Here, we present a high-resolution 3D in vivo brain atlas of synaptic density in the human brain. In the healthy human brain, distinctive cortical and subcortical gradients of synapse density reflect functional topography and hierarchical order from core sensory to higher-order integrative areas - a distribution that diverges from SV2A mRNA patterns. This brain atlas will help advance our understanding of human brain physiology and the pathogenesis of brain disorders, serving as a pivotal tool for future research in clinical, translational and comparative neuroscience .
Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial
Borchmann P, Ferdinandus J, Schneider G, Moccia A, Greil R, Hertzberg M, Schaub V, Hüttmann A, Keil F, Dierlamm J, Hänel M, Novak U, Meissner J, Zimmermann A, Mathas S, Zijlstra JM, Fosså A, Viardot A, Hertenstein B, Martin S, Giri P, Scholl S, Topp MS, Jung W, Vucinic V, Beck HJ, Kerkhoff A, Unger B, Rank A, Schroers R, Zum Büschenfelde CM, de Wit M, Trautmann-Grill K, Kamper P, Molin D, Kreissl S, Kaul H, von Tresckow B, Borchmann S, Behringer K, Fuchs M, Rosenwald A, Klapper W, Eich HT, Baues C, Zomas A, Hallek M, Dietlein M, Kobe C, Diehl V, , , , and
Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial
Borchmann P, Ferdinandus J, Schneider G, Moccia A, Greil R, Hertzberg M, Schaub V, Hüttmann A, Keil F, Dierlamm J, Hänel M, Novak U, Meissner J, Zimmermann A, Mathas S, Zijlstra JM, Fosså A, Viardot A, Hertenstein B, Martin S, Giri P, Scholl S, Topp MS, Jung W, Vucinic V, Beck HJ, Kerkhoff A, Unger B, Rank A, Schroers R, Zum Büschenfelde CM, de Wit M, Trautmann-Grill K, Kamper P, Molin D, Kreissl S, Kaul H, von Tresckow B, Borchmann S, Behringer K, Fuchs M, Rosenwald A, Klapper W, Eich HT, Baues C, Zomas A, Hallek M, Dietlein M, Kobe C, Diehl V, , , , and
Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles.
Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme
Vanhove C, Koole M, Fragoso Costa P, Schottelius M, Mannheim J, Kuntner C, Warnock G, McDougald W, Tavares A and Bernsen M
Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme
Vanhove C, Koole M, Fragoso Costa P, Schottelius M, Mannheim J, Kuntner C, Warnock G, McDougald W, Tavares A and Bernsen M
The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment. The larger the variability of the imaging endpoint, the more animals are needed to be able to observe statistically significant differences between groups. Therefore, preclinical imaging requires quality control procedures to maintain reliability, reproducibility, and repeatability of imaging procedures, and to ensure the accuracy and precision of SPECT and PET quantification. While the Physics Committee of the European Association of Nuclear Medicine (EANM) has already published excellent procedure guidelines for Routine Quality Control Recommendations for Nuclear Medicine Instrumentation that also includes procedures for small animal PET systems, and important steps have already been made concerning preclinical quality control aspects, this new guideline provides a review and update of these previous guidelines such that guidelines are also adapted to new technological developments.
Correction to: EANM perspectives for CZT SPECT in brain applications
Verger A, Cecchin D, Guedj E, Albert NL, Brendel M, Fraioli F, Tolboom N, Traub-Weidinger T, Yakushev I, Van Weehaeghe D, Fernandez PA, Garibotto V and Imbert L
Correction to: EANM perspectives for CZT SPECT in brain applications
Verger A, Cecchin D, Guedj E, Albert NL, Brendel M, Fraioli F, Tolboom N, Traub-Weidinger T, Yakushev I, Van Weehaeghe D, Fernandez PA, Garibotto V and Imbert L
Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study
Baxi S, Vohra S, Hong A, Mulholland N, Heuschkel M, Dahlhoff G, Cardaci G, Mirzaei S and Sathekge M
Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study
Baxi S, Vohra S, Hong A, Mulholland N, Heuschkel M, Dahlhoff G, Cardaci G, Mirzaei S and Sathekge M
Nonmelanoma skin cancer and its treatment represent a significant global cancer burden for health care systems and patients. Rhenium skin cancer therapy (Rhenium SCT) is a novel noninvasive radionuclide nonmelanoma skin cancer treatment, which can be provided in a single outpatient session. The aim of this prospective, multicenter, single-arm, international, phase IV study (EPIC-Skin) is to assess clinic- and patient-reported outcomes of Rhenium SCT as a treatment for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Eligible patients had biopsy-proven stage I or stage II BCC or SCC lesions no more than 3 mm deep and no larger than 8 cm in area. Rhenium SCT resin was applied to an adhesive foil affixed to the target lesion in a single session. Interim efficacy and safety analysis were planned once 50% of target patients had recorded a 6-mo follow-up visit. Primary outcome is the proportion of lesions achieving complete response using modified RECIST. Secondary and other outcome measures include patient-reported quality of life (QoL), treatment comfort, and cosmesis. A total of 182 patients was enrolled and administered Rhenium SCT (50 Gy dose to deepest point of target) to at least 1 BCC or SCC. Of 81 patients who reached the 6-mo posttreatment follow-up, it was found that 97.2% (103/106) of lesions showed complete responses and 2.8% (3/106) had partial responses. Improvements in QoL were also reported, whereas no patients reported any pain or discomfort during treatment. Adverse events were reported in 15.9% (29/182) of patients and were rated grade 1 ( = 19), grade 2 ( = 9), or grade 3 ( = 1). This preliminary analysis of the EPIC-Skin study indicates that Rhenium SCT is safe and effective for the treatment of BCC and SCC and is associated with significant QoL improvements. It will be particularly beneficial for lesions that are difficult to treat surgically because of size and location. It is also beneficial for patients with comorbidities or those unable to receive conventional fractionated radiotherapy.
Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR)
Noebauer-Huhmann IM, Vanhoenacker FM, Vilanova JC, Tagliafico AS, Weber MA, Lalam RK, Grieser T, Nikodinovska VV, de Rooy JWJ, Papakonstantinou O, Mccarthy C, Sconfienza LM, Verstraete K, Martel-Villagrán J, Szomolanyi P, Lecouvet FE, Afonso D, Albtoush OM, Aringhieri G, Arkun R, Aström G, Bazzocchi A, Botchu R, Breitenseher M, Chaudhary S, Dalili D, Davies M, de Jonge MC, Mete BD, Fritz J, Gielen JLMA, Hide G, Isaac A, Ivanoski S, Mansour RM, Muntaner-Gimbernat L, Navas A, O Donnell P, Örgüç Ş, Rennie WJ, Resano S, Robinson P, Sanal HT, Ter Horst SAJ, van Langevelde K, Wörtler K, Koelz M, Panotopoulos J, Windhager R and Bloem JL
Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR)
Noebauer-Huhmann IM, Vanhoenacker FM, Vilanova JC, Tagliafico AS, Weber MA, Lalam RK, Grieser T, Nikodinovska VV, de Rooy JWJ, Papakonstantinou O, Mccarthy C, Sconfienza LM, Verstraete K, Martel-Villagrán J, Szomolanyi P, Lecouvet FE, Afonso D, Albtoush OM, Aringhieri G, Arkun R, Aström G, Bazzocchi A, Botchu R, Breitenseher M, Chaudhary S, Dalili D, Davies M, de Jonge MC, Mete BD, Fritz J, Gielen JLMA, Hide G, Isaac A, Ivanoski S, Mansour RM, Muntaner-Gimbernat L, Navas A, O Donnell P, Örgüç Ş, Rennie WJ, Resano S, Robinson P, Sanal HT, Ter Horst SAJ, van Langevelde K, Wörtler K, Koelz M, Panotopoulos J, Windhager R and Bloem JL
The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls.
Recent Advances in the Diagnosis of Alzheimer's Disease: A Brief Overview of Tau PET Tracers in Nuclear Medicine
Aghahosseini F, Salehi Y, Farzanefar S, Bakhshi Kashi M, Eppard E, Ahmadzadehfar H, Mirzaei S, Vahidfar N and Aghanejad A
Recent Advances in the Diagnosis of Alzheimer's Disease: A Brief Overview of Tau PET Tracers in Nuclear Medicine
Aghahosseini F, Salehi Y, Farzanefar S, Bakhshi Kashi M, Eppard E, Ahmadzadehfar H, Mirzaei S, Vahidfar N and Aghanejad A
Dementia (the most common cause of Alzheimer's disease) is defined as a chronic or progressive syndrome with disturbance of multiple cortical functions, the most important of them including memory, learning capacity, comprehension, orientation, calculation, language, and judgement. These cognitive impairments affect the quality of life, behavior, and social relations. Techniques of nuclear medicine provide feasible ways to record the intracellular alterations of disease and deficiencies. In these non-invasive manners, the hippocampal-neocortical disconnection may partly explain the hypo-metabolism incident found in Alzheimer's disease. Based on this fact, the study of all these mechanisms of action is conceivable and achievable by radiopharmaceuticals. This review is aimed at the presentation of radiopharmaceuticals that are developed for the detection of Alzheimer's disease in preclinical and clinical trials.
Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects
Handschuh PA, Reed MB, Murgaš M, Vraka C, Kaufmann U, Nics L, Klöbl M, Ozenil M, Konadu ME, Patronas EM, Spurny-Dworak B, Hahn A, Hacker M, Spies M, Baldinger-Melich P, Kranz GS and Lanzenberger R
Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects
Handschuh PA, Reed MB, Murgaš M, Vraka C, Kaufmann U, Nics L, Klöbl M, Ozenil M, Konadu ME, Patronas EM, Spurny-Dworak B, Hahn A, Hacker M, Spies M, Baldinger-Melich P, Kranz GS and Lanzenberger R
MAO-A catalyzes the oxidative degradation of monoamines and is thus implicated in sex-specific neuroplastic processes that influence gray matter (GM) density (GMD) and microstructure (GMM). Given the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy (GHT) represent a valuable cohort to potentially investigate sex steroid-induced changes of GM and concomitant MAO-A density. Here, we investigated the effects of GHT over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men underwent two MRI scans in a longitudinal design. PET scans using [C]harmine were performed before each MRI session in a subset of 35 individuals. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: p < 0.025). In terms of MAO-A distribution volume, no significant effects were found. Additionally, the sexual desire inventory (SDI) was applied to assess GHT-induced changes in sexual desire, showing an increase of SDI scores among transgender men. Changes in the GMD of the bilateral insula showed a moderate correlation to SDI scores (rho = - 0.62, p = 0.047). The present results are indicative of a reliable influence of gender-affirming hormone therapy on 1) GMD and GMM following an interregional pattern and 2) sexual desire specifically among transgender men.
Teilbereich PET
Sedation-free pediatric [F]FDG imaging on totalbody PET/CT with the assistance of artificial intelligence
Zhou X, Xue S, Li L, Seifert R, Dong S, Chen R, Huang G, Rominger A, Liu J and Shi K
Sedation-free pediatric [F]FDG imaging on totalbody PET/CT with the assistance of artificial intelligence
Zhou X, Xue S, Li L, Seifert R, Dong S, Chen R, Huang G, Rominger A, Liu J and Shi K
While sedation is routinely used in pediatric PET examinations to preserve diagnostic quality, it may result in side effects and may affect the radiotracer's biodistribution. This study aims to investigate the feasibility of sedation-free pediatric PET imaging using ultra-fast total-body (TB) PET scanners and deep learning (DL)-based attenuation and scatter correction (ASC).
Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial
Borchmann P, Ferdinandus J, Schneider G, Moccia A, Greil R, Hertzberg M, Schaub V, Hüttmann A, Keil F, Dierlamm J, Hänel M, Novak U, Meissner J, Zimmermann A, Mathas S, Zijlstra JM, Fosså A, Viardot A, Hertenstein B, Martin S, Giri P, Scholl S, Topp MS, Jung W, Vucinic V, Beck HJ, Kerkhoff A, Unger B, Rank A, Schroers R, Zum Büschenfelde CM, de Wit M, Trautmann-Grill K, Kamper P, Molin D, Kreissl S, Kaul H, von Tresckow B, Borchmann S, Behringer K, Fuchs M, Rosenwald A, Klapper W, Eich HT, Baues C, Zomas A, Hallek M, Dietlein M, Kobe C, Diehl V, , , , and
Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial
Borchmann P, Ferdinandus J, Schneider G, Moccia A, Greil R, Hertzberg M, Schaub V, Hüttmann A, Keil F, Dierlamm J, Hänel M, Novak U, Meissner J, Zimmermann A, Mathas S, Zijlstra JM, Fosså A, Viardot A, Hertenstein B, Martin S, Giri P, Scholl S, Topp MS, Jung W, Vucinic V, Beck HJ, Kerkhoff A, Unger B, Rank A, Schroers R, Zum Büschenfelde CM, de Wit M, Trautmann-Grill K, Kamper P, Molin D, Kreissl S, Kaul H, von Tresckow B, Borchmann S, Behringer K, Fuchs M, Rosenwald A, Klapper W, Eich HT, Baues C, Zomas A, Hallek M, Dietlein M, Kobe C, Diehl V, , , , and
Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles.
Fibroblast Activation Protein-Directed Imaging Outperforms F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial
Kessler L, Schwaning F, Metzenmacher M, Pabst K, Siveke J, Trajkovic-Arsic M, Schaarschmidt B, Wiesweg M, Aigner C, Plönes T, Darwiche K, Bölükbas S, Stuschke M, Umutlu L, Nader M, Theegarten D, Hamacher R, Eberhardt WEE, Schuler M, Herrmann K, Fendler WP and Hautzel H
Fibroblast Activation Protein-Directed Imaging Outperforms F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial
Kessler L, Schwaning F, Metzenmacher M, Pabst K, Siveke J, Trajkovic-Arsic M, Schaarschmidt B, Wiesweg M, Aigner C, Plönes T, Darwiche K, Bölükbas S, Stuschke M, Umutlu L, Nader M, Theegarten D, Hamacher R, Eberhardt WEE, Schuler M, Herrmann K, Fendler WP and Hautzel H
The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a Ga-FAPI46 PET observational trial (NCT04571086). Of 43 eligible patients with suspected or proven malignant mesothelioma, 41 could be included in the data analysis of the Ga-FAPI46 PET observational trial. All patients underwent Ga-FAPI46 PET/CT, contrast-enhanced CT, and F-FDG PET/CT. The primary study endpoint was the association of Ga-FAPI46 PET uptake intensity and histopathologic FAP expression. Furthermore, secondary endpoints were detection rate and sensitivity, specificity, and positive and negative predictive values as compared with F-FDG PET/CT. Datasets were interpreted by 2 masked readers. The primary endpoint was met, and the association between Ga-FAPI46 SUV or SUV and histopathologic FAP expression was significant (SUV: = 0.49, = 0.037; SUV: = 0.51, = 0.030).Ga-FAPI46 and F-FDG showed similar sensitivity by histopathologic validation on a per-patient (100.0% vs. 97.3%) and per region (98.0% vs. 95.9%) basis. Per-region analysis revealed higher Ga-FAPI46 than F-FDG specificity (81.1% vs. 36.8%) and positive predictive value (87.5% vs. 66.2%). We confirm an association of Ga-FAPI46 uptake and histopathologic FAP expression in mesothelioma patients. Additionally, we report high sensitivity and superior specificity and positive predictive value for Ga-FAPI46 versus F-FDG.
An in vivo high-resolution human brain atlas of synaptic density
Johansen A, Beliveau V, Colliander E, Raval NR, Dam VH, Gillings N, Aznar S, Svarer C, Plavén-Sigray P and Knudsen GM
An in vivo high-resolution human brain atlas of synaptic density
Johansen A, Beliveau V, Colliander E, Raval NR, Dam VH, Gillings N, Aznar S, Svarer C, Plavén-Sigray P and Knudsen GM
Synapses are fundamental to the function of the central nervous system and are implicated in a number of brain disorders. Despite their pivotal role, a comprehensive imaging resource detailing the distribution of synapses in the human brain has been lacking until now. Here, we employ high-resolution PET neuroimaging in healthy humans (17F/16M) to create a 3D atlas of the synaptic marker Synaptic Vesicle glycoprotein 2A (SV2A). Calibration to absolute density values (pmol/mL) was achieved by leveraging postmortem human brain autoradiography data. The atlas unveils distinctive cortical and subcortical gradients of synapse density that reflect functional topography and hierarchical order from core sensory to higher-order integrative areas - a distribution that diverges from SV2A mRNA patterns. Furthermore, we find a positive association between IQ and SV2A density in several higher-order cortical areas. This new resource will help advance our understanding of brain physiology and the pathogenesis of brain disorders, serving as a pivotal tool for future neuroscience research. Here, we present a high-resolution 3D in vivo brain atlas of synaptic density in the human brain. In the healthy human brain, distinctive cortical and subcortical gradients of synapse density reflect functional topography and hierarchical order from core sensory to higher-order integrative areas - a distribution that diverges from SV2A mRNA patterns. This brain atlas will help advance our understanding of human brain physiology and the pathogenesis of brain disorders, serving as a pivotal tool for future research in clinical, translational and comparative neuroscience .
Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme
Vanhove C, Koole M, Fragoso Costa P, Schottelius M, Mannheim J, Kuntner C, Warnock G, McDougald W, Tavares A and Bernsen M
Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme
Vanhove C, Koole M, Fragoso Costa P, Schottelius M, Mannheim J, Kuntner C, Warnock G, McDougald W, Tavares A and Bernsen M
The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment. The larger the variability of the imaging endpoint, the more animals are needed to be able to observe statistically significant differences between groups. Therefore, preclinical imaging requires quality control procedures to maintain reliability, reproducibility, and repeatability of imaging procedures, and to ensure the accuracy and precision of SPECT and PET quantification. While the Physics Committee of the European Association of Nuclear Medicine (EANM) has already published excellent procedure guidelines for Routine Quality Control Recommendations for Nuclear Medicine Instrumentation that also includes procedures for small animal PET systems, and important steps have already been made concerning preclinical quality control aspects, this new guideline provides a review and update of these previous guidelines such that guidelines are also adapted to new technological developments.
Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study
Baxi S, Vohra S, Hong A, Mulholland N, Heuschkel M, Dahlhoff G, Cardaci G, Mirzaei S and Sathekge M
Effectiveness and Patient Experiences of Rhenium Skin Cancer Therapy for Nonmelanoma Skin Cancer: Interim Results from the EPIC-Skin Study
Baxi S, Vohra S, Hong A, Mulholland N, Heuschkel M, Dahlhoff G, Cardaci G, Mirzaei S and Sathekge M
Nonmelanoma skin cancer and its treatment represent a significant global cancer burden for health care systems and patients. Rhenium skin cancer therapy (Rhenium SCT) is a novel noninvasive radionuclide nonmelanoma skin cancer treatment, which can be provided in a single outpatient session. The aim of this prospective, multicenter, single-arm, international, phase IV study (EPIC-Skin) is to assess clinic- and patient-reported outcomes of Rhenium SCT as a treatment for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Eligible patients had biopsy-proven stage I or stage II BCC or SCC lesions no more than 3 mm deep and no larger than 8 cm in area. Rhenium SCT resin was applied to an adhesive foil affixed to the target lesion in a single session. Interim efficacy and safety analysis were planned once 50% of target patients had recorded a 6-mo follow-up visit. Primary outcome is the proportion of lesions achieving complete response using modified RECIST. Secondary and other outcome measures include patient-reported quality of life (QoL), treatment comfort, and cosmesis. A total of 182 patients was enrolled and administered Rhenium SCT (50 Gy dose to deepest point of target) to at least 1 BCC or SCC. Of 81 patients who reached the 6-mo posttreatment follow-up, it was found that 97.2% (103/106) of lesions showed complete responses and 2.8% (3/106) had partial responses. Improvements in QoL were also reported, whereas no patients reported any pain or discomfort during treatment. Adverse events were reported in 15.9% (29/182) of patients and were rated grade 1 ( = 19), grade 2 ( = 9), or grade 3 ( = 1). This preliminary analysis of the EPIC-Skin study indicates that Rhenium SCT is safe and effective for the treatment of BCC and SCC and is associated with significant QoL improvements. It will be particularly beneficial for lesions that are difficult to treat surgically because of size and location. It is also beneficial for patients with comorbidities or those unable to receive conventional fractionated radiotherapy.
Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR)
Noebauer-Huhmann IM, Vanhoenacker FM, Vilanova JC, Tagliafico AS, Weber MA, Lalam RK, Grieser T, Nikodinovska VV, de Rooy JWJ, Papakonstantinou O, Mccarthy C, Sconfienza LM, Verstraete K, Martel-Villagrán J, Szomolanyi P, Lecouvet FE, Afonso D, Albtoush OM, Aringhieri G, Arkun R, Aström G, Bazzocchi A, Botchu R, Breitenseher M, Chaudhary S, Dalili D, Davies M, de Jonge MC, Mete BD, Fritz J, Gielen JLMA, Hide G, Isaac A, Ivanoski S, Mansour RM, Muntaner-Gimbernat L, Navas A, O Donnell P, Örgüç Ş, Rennie WJ, Resano S, Robinson P, Sanal HT, Ter Horst SAJ, van Langevelde K, Wörtler K, Koelz M, Panotopoulos J, Windhager R and Bloem JL
Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR)
Noebauer-Huhmann IM, Vanhoenacker FM, Vilanova JC, Tagliafico AS, Weber MA, Lalam RK, Grieser T, Nikodinovska VV, de Rooy JWJ, Papakonstantinou O, Mccarthy C, Sconfienza LM, Verstraete K, Martel-Villagrán J, Szomolanyi P, Lecouvet FE, Afonso D, Albtoush OM, Aringhieri G, Arkun R, Aström G, Bazzocchi A, Botchu R, Breitenseher M, Chaudhary S, Dalili D, Davies M, de Jonge MC, Mete BD, Fritz J, Gielen JLMA, Hide G, Isaac A, Ivanoski S, Mansour RM, Muntaner-Gimbernat L, Navas A, O Donnell P, Örgüç Ş, Rennie WJ, Resano S, Robinson P, Sanal HT, Ter Horst SAJ, van Langevelde K, Wörtler K, Koelz M, Panotopoulos J, Windhager R and Bloem JL
The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls.
Recent Advances in the Diagnosis of Alzheimer's Disease: A Brief Overview of Tau PET Tracers in Nuclear Medicine
Aghahosseini F, Salehi Y, Farzanefar S, Bakhshi Kashi M, Eppard E, Ahmadzadehfar H, Mirzaei S, Vahidfar N and Aghanejad A
Recent Advances in the Diagnosis of Alzheimer's Disease: A Brief Overview of Tau PET Tracers in Nuclear Medicine
Aghahosseini F, Salehi Y, Farzanefar S, Bakhshi Kashi M, Eppard E, Ahmadzadehfar H, Mirzaei S, Vahidfar N and Aghanejad A
Dementia (the most common cause of Alzheimer's disease) is defined as a chronic or progressive syndrome with disturbance of multiple cortical functions, the most important of them including memory, learning capacity, comprehension, orientation, calculation, language, and judgement. These cognitive impairments affect the quality of life, behavior, and social relations. Techniques of nuclear medicine provide feasible ways to record the intracellular alterations of disease and deficiencies. In these non-invasive manners, the hippocampal-neocortical disconnection may partly explain the hypo-metabolism incident found in Alzheimer's disease. Based on this fact, the study of all these mechanisms of action is conceivable and achievable by radiopharmaceuticals. This review is aimed at the presentation of radiopharmaceuticals that are developed for the detection of Alzheimer's disease in preclinical and clinical trials.
Hodgkin lymphoma: hypodense lesions in mediastinal masses
Damek A, Kurch L, Franke FC, Attarbaschi A, Beishuizen A, Cepelova M, Ceppi F, Daw S, Dieckmann K, Fernández-Teijeiro A, Feuchtinger T, Flerlage JE, Fosså A, Georgi TW, Hasenclever D, Hraskova A, Karlen J, Klekawka T, Kluge R, Körholz D, Landman-Parker J, Leblanc T, Mauz-Körholz C, Metzler M, Pears J, Steglich J, Uyttebroeck A, Vordermark D, Wallace WH, Wohlgemuth WA and Stoevesandt D
Hodgkin lymphoma: hypodense lesions in mediastinal masses
Damek A, Kurch L, Franke FC, Attarbaschi A, Beishuizen A, Cepelova M, Ceppi F, Daw S, Dieckmann K, Fernández-Teijeiro A, Feuchtinger T, Flerlage JE, Fosså A, Georgi TW, Hasenclever D, Hraskova A, Karlen J, Klekawka T, Kluge R, Körholz D, Landman-Parker J, Leblanc T, Mauz-Körholz C, Metzler M, Pears J, Steglich J, Uyttebroeck A, Vordermark D, Wallace WH, Wohlgemuth WA and Stoevesandt D
Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with mediastinal involvement from the EuroNet-PHL-C1 trial and explored correlations of HDV with patient characteristics, mediastinal tumor volume and progression-free survival. HDV occurred in 350 of 1178 patients (29.7%), typically in larger mediastinal volumes. There were different patterns in appearance with single lesions found in 243 patients (69.4%), multiple lesions in 107 patients (30.6%). Well delineated lesions were found in 248 cases (70.1%), diffuse lesions were seen in 102 cases (29.1%). Clinically, B symptoms occurred more often in patients with HDV (47.7% compared to 35.0% without HDV (p = 0.039)) and patients with HDV tended to be in higher risk groups. Inadequate overall early-F-FDG-PET-response was strongly correlated with the occurrence of hypodense lesions (p < 0.001). Patients with total HDV > 40 ml (n = 80) had a 5 year PFS of 79.6% compared to 89.7% (p = 0.01) in patients with HDV < 40 ml or no HDV. This difference in PFS is not caused by treatment group alone. HDV is a common phenomenon in HL with mediastinal involvement.
Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects
Handschuh PA, Reed MB, Murgaš M, Vraka C, Kaufmann U, Nics L, Klöbl M, Ozenil M, Konadu ME, Patronas EM, Spurny-Dworak B, Hahn A, Hacker M, Spies M, Baldinger-Melich P, Kranz GS and Lanzenberger R
Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects
Handschuh PA, Reed MB, Murgaš M, Vraka C, Kaufmann U, Nics L, Klöbl M, Ozenil M, Konadu ME, Patronas EM, Spurny-Dworak B, Hahn A, Hacker M, Spies M, Baldinger-Melich P, Kranz GS and Lanzenberger R
MAO-A catalyzes the oxidative degradation of monoamines and is thus implicated in sex-specific neuroplastic processes that influence gray matter (GM) density (GMD) and microstructure (GMM). Given the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy (GHT) represent a valuable cohort to potentially investigate sex steroid-induced changes of GM and concomitant MAO-A density. Here, we investigated the effects of GHT over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men underwent two MRI scans in a longitudinal design. PET scans using [C]harmine were performed before each MRI session in a subset of 35 individuals. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: p < 0.025). In terms of MAO-A distribution volume, no significant effects were found. Additionally, the sexual desire inventory (SDI) was applied to assess GHT-induced changes in sexual desire, showing an increase of SDI scores among transgender men. Changes in the GMD of the bilateral insula showed a moderate correlation to SDI scores (rho = - 0.62, p = 0.047). The present results are indicative of a reliable influence of gender-affirming hormone therapy on 1) GMD and GMM following an interregional pattern and 2) sexual desire specifically among transgender men.
Teilbereich SPECT
Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme
Vanhove C, Koole M, Fragoso Costa P, Schottelius M, Mannheim J, Kuntner C, Warnock G, McDougald W, Tavares A and Bernsen M
Preclinical SPECT and PET: Joint EANM and ESMI procedure guideline for implementing an efficient quality control programme
Vanhove C, Koole M, Fragoso Costa P, Schottelius M, Mannheim J, Kuntner C, Warnock G, McDougald W, Tavares A and Bernsen M
The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment. The larger the variability of the imaging endpoint, the more animals are needed to be able to observe statistically significant differences between groups. Therefore, preclinical imaging requires quality control procedures to maintain reliability, reproducibility, and repeatability of imaging procedures, and to ensure the accuracy and precision of SPECT and PET quantification. While the Physics Committee of the European Association of Nuclear Medicine (EANM) has already published excellent procedure guidelines for Routine Quality Control Recommendations for Nuclear Medicine Instrumentation that also includes procedures for small animal PET systems, and important steps have already been made concerning preclinical quality control aspects, this new guideline provides a review and update of these previous guidelines such that guidelines are also adapted to new technological developments.
Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance
Lauri C, Noriega-Álvarez E, Chakravartty RM, Gheysens O, Glaudemans AWJM, Slart RHJA, Kwee TC, Lecouvet F, Panagiotidis E, Zhang-Yin J, Martinez JLL, Lipsky BA, Uccioli L and Signore A
Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance
Lauri C, Noriega-Álvarez E, Chakravartty RM, Gheysens O, Glaudemans AWJM, Slart RHJA, Kwee TC, Lecouvet F, Panagiotidis E, Zhang-Yin J, Martinez JLL, Lipsky BA, Uccioli L and Signore A
Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings.
Correction to: EANM perspectives for CZT SPECT in brain applications
Verger A, Cecchin D, Guedj E, Albert NL, Brendel M, Fraioli F, Tolboom N, Traub-Weidinger T, Yakushev I, Van Weehaeghe D, Fernandez PA, Garibotto V and Imbert L
Correction to: EANM perspectives for CZT SPECT in brain applications
Verger A, Cecchin D, Guedj E, Albert NL, Brendel M, Fraioli F, Tolboom N, Traub-Weidinger T, Yakushev I, Van Weehaeghe D, Fernandez PA, Garibotto V and Imbert L
Prognostic Value of [Tc]Tc-DPD Quantitative SPECT/CT in Patients with Suspected and Confirmed Amyloid Transthyretin-Related Cardiomyopathy and Preserved Left Ventricular Function
Caobelli F, Gözlügöl N, Bakula A, Rominger A, Schepers R, Stortecky S, Hunziker Munsch L, Dobner S and Gräni C
Prognostic Value of [Tc]Tc-DPD Quantitative SPECT/CT in Patients with Suspected and Confirmed Amyloid Transthyretin-Related Cardiomyopathy and Preserved Left Ventricular Function
Caobelli F, Gözlügöl N, Bakula A, Rominger A, Schepers R, Stortecky S, Hunziker Munsch L, Dobner S and Gräni C
Quantitative Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ([Tc]Tc-DPD) SPECT may be used for risk-stratifying patients with amyloid transthyretin-related cardiomyopathy (ATTR-CM). We aimed to analyze the predictive value of quantitative [Tc]Tc-DPD SPECT/CT in suspected and confirmed ATTR-CM according to different disease stages. The study enrolled consecutive patients with suspected ATTR-CM who were referred to a single tertiary center and underwent quantitative [Tc]Tc-DPD SPECT/CT allowing SUV and SUV analysis. Patients were divided into 2 groups according to left ventricular ejection fraction (LVEF) at baseline (i.e., ≥50% and <50%). Clinical, laboratory, and echocardiographic parameters and major adverse cardiac events (i.e., all-cause death, sustained ventricular tachyarrhythmia, hospitalization for heart failure, implantation of a cardioverter defibrillator) were investigated for any correlation with quantitative uptake values. In total, 144 patients with suspected ATTR-CM were included in the study (98 with LVEF ≥ 50% and 46 with LVEF < 50%), of whom 99 were diagnosed with ATTR-CM (68.8%; 69 with LVEF ≥ 50% and 30 with LVEF < 50%). A myocardial SUV of at least 7 was predictive of major adverse cardiac events at 21.9 ± 13.0 mo of follow-up (hazard ratio, 2.875; 95% CI, 1.23-6.71; = 0.015) in patients with suspected or confirmed ATTR-CM (global χ = 6.892, = 0.02) and an LVEF of at least 50%. SUV was not predictive in patients with an LVEF of less than 50% and suspected or confirmed ATTR-CM. In patients with suspected or confirmed ATTR-CM and preserved LVEF, representing an early disease stage, quantitative [Tc]Tc-DPD SPECT should be considered to improve early-stage risk stratification.
EANM perspectives for CZT SPECT in brain applications
Verger A, Cecchin D, Guedj E, Albert NL, Brendel M, Fraioli F, Tolboom N, Traub-Weidinger T, Yakushev I, Van Weehaeghe D, Fernandez PA, Garibotto V and Imbert L
EANM perspectives for CZT SPECT in brain applications
Verger A, Cecchin D, Guedj E, Albert NL, Brendel M, Fraioli F, Tolboom N, Traub-Weidinger T, Yakushev I, Van Weehaeghe D, Fernandez PA, Garibotto V and Imbert L
Transarterial Radioembolization (TARE) Global Practice Patterns: An International Survey by the Cardiovascular and Interventional Radiology Society of Europe (CIRSE)
Keane G, Lam M, Braat A, Bruijnen R, Kaufmann N, de Jong H and Smits M
Transarterial Radioembolization (TARE) Global Practice Patterns: An International Survey by the Cardiovascular and Interventional Radiology Society of Europe (CIRSE)
Keane G, Lam M, Braat A, Bruijnen R, Kaufmann N, de Jong H and Smits M
An international survey was conducted by the Cardiovascular Interventional Radiological Society of Europe (CIRSE) to evaluate radioembolization practice and capture opinions on real-world clinical and technical aspects of this therapy.
Pre-therapy PET-based voxel-wise dosimetry prediction by characterizing intra-organ heterogeneity in PSMA-directed radiopharmaceutical theranostics
Xue S, Gafita A, Zhao Y, Mercolli L, Cheng F, Rauscher I, D'Alessandria C, Seifert R, Afshar-Oromieh A, Rominger A, Eiber M and Shi K
Pre-therapy PET-based voxel-wise dosimetry prediction by characterizing intra-organ heterogeneity in PSMA-directed radiopharmaceutical theranostics
Xue S, Gafita A, Zhao Y, Mercolli L, Cheng F, Rauscher I, D'Alessandria C, Seifert R, Afshar-Oromieh A, Rominger A, Eiber M and Shi K
Treatment planning through the diagnostic dimension of theranostics provides insights into predicting the absorbed dose of RPT, with the potential to individualize radiation doses for enhancing treatment efficacy. However, existing studies focusing on dose prediction from diagnostic data often rely on organ-level estimations, overlooking intra-organ variations. This study aims to characterize the intra-organ theranostic heterogeneity and utilize artificial intelligence techniques to localize them, i.e. to predict voxel-wise absorbed dose map based on pre-therapy PET.
Whole brain pattern of iron accumulation in REM sleep behavior disorder
Varga Z, Keller J, Robinson SD, Serranova T, Nepozitek J, Zogala D, Trnka J, Ruzicka E, Sonka K and Dusek P
Whole brain pattern of iron accumulation in REM sleep behavior disorder
Varga Z, Keller J, Robinson SD, Serranova T, Nepozitek J, Zogala D, Trnka J, Ruzicka E, Sonka K and Dusek P
Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.
Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103
Happl B, Balber T, Heffeter P, Denk C, Welch JM, Köster U, Alliot C, Bonraisin AC, Brandt M, Haddad F, Sterba JH, Kandioller W, Mitterhauser M, Hacker M, Keppler BK and Mindt TL
Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103
Happl B, Balber T, Heffeter P, Denk C, Welch JM, Köster U, Alliot C, Bonraisin AC, Brandt M, Haddad F, Sterba JH, Kandioller W, Mitterhauser M, Hacker M, Keppler BK and Mindt TL
BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.) [Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 (Ru; β, γ) and ruthenium-97 (Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a. [Ru]BOLD-100 (3 and 30 mg kg) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally, autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [Ru]BOLD-100.
Amide-to-Triazole Switch in Somatostatin-14-Based Radioligands: Impact on Receptor Affinity and In Vivo Stability
Guarrochena X, Kanellopoulos P, Stingeder A, Rečnik LM, Feiner IVJ, Brandt M, Kandioller W, Maina T, Nock BA and Mindt TL
Amide-to-Triazole Switch in Somatostatin-14-Based Radioligands: Impact on Receptor Affinity and In Vivo Stability
Guarrochena X, Kanellopoulos P, Stingeder A, Rečnik LM, Feiner IVJ, Brandt M, Kandioller W, Maina T, Nock BA and Mindt TL
The use of metabolically stabilized, radiolabeled somatostatin (SST) analogs ([Ga]Ga/[Lu]Lu-DOTA-TATE/TOC/NOC) is well established in nuclear medicine. Despite the pivotal role of these radioligands in the diagnosis and therapy of neuroendocrine tumors (NETs), their inability to interact with all five somatostatin receptors (SSTR) limits their clinical potential. [In]In-AT2S is a radiolabeled DOTA-conjugate derived from the parent peptide SST-14 that exhibits high binding affinity to all SSTR subtypes, but its poor metabolic stability represents a serious disadvantage for clinical use. In order to address this issue, we have replaced strategic -amide bonds of [In]In-AT2S with metabolically stable 1,4-disubstituted 1,2,3-triazole bioisosteres. From the five cyclic triazolo-peptidomimetics investigated, only [In]In-XG1 combined a preserved nanomolar affinity for the SSTR subtypes in vitro and an improved stability in vivo (up to 17% of intact peptide 5 min postinjection (pi) versus 6% for [In]In-AT2S). The involvement of neprilysin (NEP) in the metabolism of [In]In-XG1 was confirmed by coadministration of Entresto, a registered antihypertensive drug, in vivo releasing the selective and potent NEP-inhibitor sacubitrilat. A pilot SPECT/CT imaging study conducted in mice bearing hSSTR-positive xenografts failed to visualize the xenografts due to the pronounced kidney uptake (>200% injected activity (IA)/g at 4 h pi), likely the result of the formation of cationic metabolites. To corroborate the imaging data, the tumors and the kidneys were excised and analyzed with a -counter. Even if receptor-specific tumor uptake for [In]In-XG1 could be confirmed (1.61% IA/g), further optimization is required to improve its pharmacokinetic properties for radiotracer development.
Teilbereich Nuklearmedizinische Therapie
Dosimetry and pharmacokinetics of [Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours
Schürrle SB, Eberlein U, Ansquer C, Beauregard JM, Durand-Gasselin L, Grønbæk H, Haug A, Hicks RJ, Lenzo NP, Navalkissoor S, Nicolas GP, Pais B, Volteau M, Wild D, McEwan A and Lassmann M
Dosimetry and pharmacokinetics of [Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours
Schürrle SB, Eberlein U, Ansquer C, Beauregard JM, Durand-Gasselin L, Grønbæk H, Haug A, Hicks RJ, Lenzo NP, Navalkissoor S, Nicolas GP, Pais B, Volteau M, Wild D, McEwan A and Lassmann M
To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs).
Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0
Albert NL, Preusser M, Traub-Weidinger T, Tolboom N, Law I, Palmer JD, Guedj E, Furtner J, Fraioli F, Huang RY, Johnson DR, Deroose CM, Herrmann K, Vogelbaum M, Chang S, Tonn JC, Weller M, Wen PY, van den Bent MJ, Verger A, Ivanidze J and Galldiks N
Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0
Albert NL, Preusser M, Traub-Weidinger T, Tolboom N, Law I, Palmer JD, Guedj E, Furtner J, Fraioli F, Huang RY, Johnson DR, Deroose CM, Herrmann K, Vogelbaum M, Chang S, Tonn JC, Weller M, Wen PY, van den Bent MJ, Verger A, Ivanidze J and Galldiks N
To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands.
Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives
Santo G, Di Santo G and Virgolini I
Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives
Santo G, Di Santo G and Virgolini I
Peptide receptor radionuclide therapy (PRRT) today is a well-established treatment strategy for patients with neuroendocrine tumors (NET). First performed already more than 30 years ago, PRRT was incorporated only in recent years into the major oncology guidelines, based on its proven efficacy and safety in clinical trials. Following the phase 3 NETTER-1 trial, which led to the final registration of the radiopharmaceutical Luthatera® for G1/G2 NET patients in 2017, the long-term results of the phase 3 NETTER-2 trial may pave the way for a new treatment option also for advanced G2/G3 patients as first-line therapy. The growing knowledge about the synergistic effect of combined therapies could also allow alternative (re)treatment options for NET patients, in order to create a tailored treatment strategy. The evolving thera(g)nostic concept could be applied for the identification of patients who might benefit from different image-guided treatment strategies. In this scenario, the use of dual tracer PET/CT in NET patients, using both [F]F-FDG/[Ga]Ga-DOTA-somatostatin analog (SSA) for diagnosis and follow-up, is under discussion and could also result in a powerful prognostic tool. In addition, alternative strategies based on different metabolic pathways, radioisotopes, or combinations of different medical approaches could be applied. A number of different promising "doors" could thus open in the near future for the treatment of NET patients - and the "key" will be thera(g)nostic!
Theranostics in Neurooncology: Heading Toward New Horizons
Tolboom N, Verger A, Albert NL, Fraioli F, Guedj E, Traub-Weidinger T, Morbelli S, Herrmann K, Zucchetta P, Plasschaert SLA, Yakushev I, Weller M, Glas M, Preusser M, Cecchin D, Barthel H and Van Weehaeghe D
Theranostics in Neurooncology: Heading Toward New Horizons
Tolboom N, Verger A, Albert NL, Fraioli F, Guedj E, Traub-Weidinger T, Morbelli S, Herrmann K, Zucchetta P, Plasschaert SLA, Yakushev I, Weller M, Glas M, Preusser M, Cecchin D, Barthel H and Van Weehaeghe D
Therapeutic approaches to brain tumors remain a challenge, with considerable limitations regarding delivery of drugs. There has been renewed and increasing interest in translating the popular theranostic approach well known from prostate and neuroendocrine cancer to neurooncology. Although far from perfect, some of these approaches show encouraging preliminary results, such as for meningioma and leptomeningeal spread of certain pediatric brain tumors. In brain metastases and gliomas, clinical results have failed to impress. Perspectives on these theranostic approaches regarding meningiomas, brain metastases, gliomas, and common pediatric brain tumors will be discussed. For each tumor entity, the general context, an overview of the literature, and future perspectives will be provided. Ongoing studies will be discussed in the supplemental materials. As most theranostic agents are unlikely to cross the blood-brain barrier, the delivery of these agents will be dependent on the successful development and clinical implementation of techniques enhancing permeability and retention. Moreover, the international community should strive toward sufficiently large and randomized studies to generate high-level evidence on theranostic approaches with radioligand therapies for central nervous system tumors.
A phase I/II study of the safety and efficacy of [Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours
Wild D, Grønbæk H, Navalkissoor S, Haug A, Nicolas GP, Pais B, Ansquer C, Beauregard JM, McEwan A, Lassmann M, Pennestri D, Volteau M, Lenzo NP and Hicks RJ
A phase I/II study of the safety and efficacy of [Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours
Wild D, Grønbæk H, Navalkissoor S, Haug A, Nicolas GP, Pais B, Ansquer C, Beauregard JM, McEwan A, Lassmann M, Pennestri D, Volteau M, Lenzo NP and Hicks RJ
We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity.
Radiobiological Assessment of Targeted Radionuclide Therapy with [Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models
Raitanen J, Barta B, Fuchs H, Hacker M, Balber T, Georg D and Mitterhauser M
Radiobiological Assessment of Targeted Radionuclide Therapy with [Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models
Raitanen J, Barta B, Fuchs H, Hacker M, Balber T, Georg D and Mitterhauser M
In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others.
Automated Synthesis of [Ga]Ga-FAPI-46 on a Scintomics GRP Synthesizer
Plhak E, Pichler C, Dittmann-Schnabel B, Gößnitzer E, Aigner RM, Stanzel S and Kvaternik H
Automated Synthesis of [Ga]Ga-FAPI-46 on a Scintomics GRP Synthesizer
Plhak E, Pichler C, Dittmann-Schnabel B, Gößnitzer E, Aigner RM, Stanzel S and Kvaternik H
[Ga]Ga-FAPI-46 is a radiolabelled fibroblast activation protein inhibitor that selectively binds to fibroblast activation protein (FAP), which is overexpressed by cancer-associated fibroblasts (CAFs) in the tumour microenvironment. In recent years, radiolabelled FAP inhibitors (FAPIs) are becoming increasingly important in cancer diagnostics and also for targeted radionuclide therapy. Because of the increasing demand for radiolabelled FAPIs, automating the synthesis of these compounds is of great interest. In this work, we present a newly programmed automatic synthesis process of [Ga]Ga-FAPI-46 on a Scintomics GRP module using two Galli Ad generators as a radionuclide source. Dedicated cassettes for the labelling of Ga-peptides were used without any modifications. The generators were connected via a three-way valve to the module and eluted automatically over a strong cation exchange (SCX) cartridge by using the vacuum pump of the synthesis module, eliminating the need to transfer the eluates into a separate vial. After a reaction step in HEPES buffer, the compound was purified by solid-phase extraction (SPE) over a Sep-Pak Light C18 cartridge. The evaluation of 10 routine syntheses of [Ga]Ga-FAPI-46 resulted in a radiochemical yield of 72.6 ± 4.9%. The radiochemical purity was 97.6 ± 0.3%, and the amount of free gallium-68 and colloid was <2%. The final product fulfilled the quality criteria, which were adapted from relevant monographs of the (Ph. Eur.). This work presents the successful preparation of multiple doses of [Ga]Ga-FAPI-46 in a GMP-compliant automated process for clinical use.
Theranostic in Nuclear Medicine - The paradigm of NET
Giammarile F
Theranostic in Nuclear Medicine - The paradigm of NET
Giammarile F
Theranostics is an emerging field in medicine that combines diagnostics and therapeutics into a single approach. Overall, theranostics represents a promising paradigm for personalized medicine, as it allows for targeted and precise treatment based on individual patient characteristics. In nuclear medicine, theranostics involves the use of radiopharmaceuticals that have both diagnostic and therapeutic properties. Moreover, theranostics in nuclear medicine offers several advantages over traditional cancer treatments. Unlike radiotherapy, in nuclear medicine the therapy is systemic that targets both primary tumors and metastatic lesions, offering a more comprehensive treatment approach. Additionally, nuclear medicine therapy has been shown to have fewer side effects compared to traditional chemotherapy, making it a more tolerable treatment option for patients. While theranostics in nuclear medicine is still a relatively new field, it has shown promising results in the treatment of neuroendocrine tumors (NETs). One example of a theranostic approach in nuclear medicine is the use of radiolabeled somatostatin analogs for the treatment of NETs. Somatostatin is a hormone that regulates the release of other hormones in the body. It also binds to somatostatin receptors, which are highly expressed in NETs. The first step in theranostics for NETs is the diagnosis and staging of the disease using a radiolabeled somatostatin analog and PET/CT imaging. This allows for the detection of the tumor and assessment of its size and location. Once the tumor has been identified, the same radiolabeled somatostatin analog can be used as a therapeutic agent. The radiopharmaceutical delivers radiation directly to the tumor cells, which destroys them while sparing surrounding healthy tissue. This is known as peptide receptor radionuclide therapy (PRRT). The use of theranostics in NETs also involves the identification of specific somatostatin receptor subtypes that are expressed in the tumor cells. This is important as different somatostatin analogs have varying affinities for different receptor subtypes. By selecting the appropriate radiolabeled somatostatin analog, clinicians can increase the specificity of the therapy, delivering radiation to the tumor cells while minimizing damage to healthy tissue. PRRT has been shown to be effective in treating NETs, particularly those that are resistant to other forms of treatment. It can also be used in combination with other therapies, such as chemotherapy and surgery, to improve outcomes. As research continues, it is likely that theranostics in nuclear medicine will become an increasingly important tool in the fight against cancer, particularly in the context of NETs, offering personalized, targeted treatment options that improve patient outcomes.
Peptide receptor radionuclide therapy combinations for neuroendocrine tumours in ongoing clinical trials: status 2023
di Santo G, Santo G, Sviridenko A and Virgolini I
Peptide receptor radionuclide therapy combinations for neuroendocrine tumours in ongoing clinical trials: status 2023
di Santo G, Santo G, Sviridenko A and Virgolini I
A growing body of literature reports on the combined use of peptide receptor radionuclide therapy (PRRT) with other anti-tumuor therapies in order to anticipate synergistic effects with perhaps increased safety issues. Combination treatments to enhance PRRT outcome are based on improved tumour perfusion, upregulation of somatostatin receptors (SSTR), radiosensitization with DNA damaging agents or targeted therapies. Several Phase 1 or 2 trials are currently recruiting patients in combined regimens. The combination of PRRT with cytotoxic chemotherapy, capecitabine and temozolomide (CAPTEM), seems to become clinically useful especially in pancreatic neuroendocrine tumours (pNETs) with acceptable safety profile. Neoadjuvant PRRT prior to surgery, PRRT combinations of intravenous and intraarterial routes of application, combinations of PRRT with differently radiolabelled (alpha, beta, Auger) SSTR-targeting agonists and antagonists, inhibitors of immune checkpoints (ICIs), poly (ADP-ribose) polymerase-1 (PARP1i), tyrosine kinase (TKI), DNA-dependent protein kinase, ribonucleotide reductase or DNA methyltransferase (DMNT) are tested in currently ongoing clinical trials. The combination with [I]I-MIBG in rare NETs (such as paraganglioma, pheochromocytoma) and new non-SSTR-targeting radioligands are used in the personalization process of treatment. The present review will provide an overview of the current status of ongoing PRRT combination treatments.
From biology to clinical practice: antiproliferative effects of somatostatin analogs in neuroendocrine neoplasms
Melhorn P, Mazal P, Wolff L, Kretschmer-Chott E, Raderer M and Kiesewetter B
From biology to clinical practice: antiproliferative effects of somatostatin analogs in neuroendocrine neoplasms
Melhorn P, Mazal P, Wolff L, Kretschmer-Chott E, Raderer M and Kiesewetter B
Somatostatin analogs (SSA), specifically octreotide and lanreotide, have demonstrated antiproliferative effects in patients with neuroendocrine tumors (NET), a group of rare malignancies of diverse origin and presentation. A prominent feature of NET cells is the expression of G protein-coupled receptors called somatostatin receptors (SSTR). Although these SSTR are not uniformly present in NET, they can be instrumental in the diagnosis and treatment of NET. Apart from their application in nuclear imaging and radionuclide therapy, SSA have proven invaluable in the treatment of hormonal syndromes associated with certain NET (antisecretory effects of SSA), but it took more than two decades to convincingly demonstrate the antiproliferative effects of SSA in metastatic NET with the two pivotal studies PROMID and CLARINET. The current review summarizes three decades of SSA treatment and provides an overview of the clinical trial landscape for SSA monotherapy and combination therapy, including clinical implications and quality of life aspects, as well as ongoing fields of research.