Publikationen

We established prognostic nomograms incorporating prostate-specific membrane antigen (PSMA) positron emission tomography (PET) parameters standardised by Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP1). Here, we develop an updated PPP2 risk score from a large international multicentre registry study.

Assessment of an antidepressant's occupancy at the serotonin transporter (SERT) in vivo using PET scans represents a demanding procedure. We evaluated novel approaches for SERT quantification to simplify the occupancy calculation. [C]DASB PET/MRI scans with bolus plus constant infusion were performed twice in 47 healthy controls and 31 patients with major depressive disorder with intravenous application of 8 mg citalopram or saline solution (randomized, cross-over, double-blind). Binding potentials (BP and BP) were estimated over time and within two radioligand equilibrium periods (before and after drug challenge). Reference occupancy was calculated as the relative decrease in post-drug BP between the placebo and citalopram scans. We introduced three methods for estimating SERT occupancy. Method 1 replaced the arterial blood sampling (BP) by reference region modeling during equilibrium timeframes (BP). Method 2 replaced the post-dose placebo equilibrium period with the pre-dose citalopram equilibrium period. Method 3 integrated aspects of both Methods 1 and 2, utilizing BP and the pre-dose citalopram equilibrium phase. The results showed equivalent occupancy values (p < 0.05) for the majority of VOIs and high agreement (max R = 0.89) between the reference (utilizing arterial blood sampling, along with the placebo and citalopram scan) and the proposed methods, indicating that they are a promising solution for simplifying occupancy estimation.

Amyloidosis is a systemic disorder characterized by amyloid fibril deposition in multiple organs, including the heart, brain, liver, kidneys, and lungs, leading to organ dysfunction and affecting survival. In cardiac amyloidosis (CA), where the heart is primarily affected, the broader impact on other organs, particularly the brain, is not fully understood. This study aimed to assess the extent of amyloid deposition across systemic organs in CA, investigate brain-organ, brain-brain and organ-organ connections, and evaluate their effects on patients' survival.

Novel diagnostic and therapeutic opportunities are needed to improve medical care and outcome of patients with brain metastases, a frequent and severe complication of several cancer types. Currently, magnetic resonance imaging (MRI) is the primary method used for detection, treatment planning and disease monitoring in patients with brain metastases, but this method has limitations. These limitations mean that MRI can inform on lesion size but cannot directly measure the activity or viability of tumor tissue. Positron emission tomography (PET) imaging, however, can visualize metabolically active tumor cells and is therefore increasingly incorporated into cancer care to assess tumor burden and response to treatment. Here, we define the PET Response Assessment in Neuro-Oncology (RANO) for brain metastasis (BM) 1.0 criteria for metabolic response assessment of brain metastases using amino acid PET. By introducing an innovative endpoint for next-generation clinical trials, the PET RANO BM 1.0 criteria aim to facilitate development of novel therapies for patients with brain metastases.

Semaglutide has demonstrated cardiovascular benefits in people with type 2 diabetes (T2D) with cardiovascular disease (CVD). Inflammation plays a well-documented role in atherosclerosis and glucagon-like peptide-1 receptor agonists, like semaglutide, have shown anti-inflammatory effects in animal and clinical studies. This trial investigated the effect of semaglutide on atherosclerotic inflammation in the carotid arteries using positron emission tomography (PET)-magnetic resonance imaging (MRI).

To evaluate the capability of hyperpolarized [1-C] pyruvate MRI to predict pathologic response to neoadjuvant treatment in multi-site abdominopelvic disease of high-grade serous ovarian cancer (HGSOC) patients and to compare C MRI and [F]-FDG PET/CT measurements for detecting early treatment response. We recruited eight patients with HGSOC in this prospective study who underwent C MRI and [F]-FDG PET/CT before and after the first cycle of neoadjuvant chemotherapy treatment (NACT). Imaging parameters were compared with clinical and histophatologic parameters.

NUT carcinoma (NUTc) is a rare, aggressive cancer characterized by rearrangement of the NUTM1 gene on chromosome 15q14. We present the case of a 32-year-old man with a persisting cough, reduced general condition, and B symptoms for 2 months. CT imaging revealed a highly suspicious mass in the right lung, infiltrating hilar structures, and the mediastinum. Staging with 18F-FDG PET/CT demonstrated pathologic 18F-FDG uptake within the tumor. Histology, immunohistochemistry, and molecular analysis confirmed NUTc of the lung. Metabolic imaging modalities may play a key role in staging, restaging, and assessing treatment response in patients with NUTc.

The rapid growth of radiopharmaceutical sciences, driven by regulatory approvals of theranostic agents and the expanding role of PET imaging, underscores the need for sustainable and green practices. While radiopharmaceuticals offer high precision and targeted therapy with minimal systemic toxicity, the field faces challenges related to increasing demand, energy consumption, and waste management. The nuclear medicine market is projected to reach $30 billion by 2030, necessitating the integration of sustainability principles such as green chemistry and green engineering into radiopharmaceutical development. Given the energy-intensive nature of radiochemical processes, these principles provide strategies for reducing environmental impact. However, radiopharmaceutical sciences require adaptations to traditional sustainability frameworks due to factors like radiation safety, speed, and automation. This perspective examines the applicability of the 12 principles of green chemistry and engineering, proposing nine key principles tailored to radiopharmaceutical sciences. These principles address waste prevention, radionuclide recycling, energy efficiency, and the adoption of cleaner irradiation technologies. As the field evolves, incorporating sustainability into training programs and research initiatives will be essential.

Radioligand therapy (RLT) has garnered significant attention due to the recent emergence of innovative and effective theranostic agents, which showed promising therapeutic and prognostic results in various cancers. Moreover, understanding the interaction between different types of radiation and biological tissues is essential for optimizing therapeutic interventions These concepts directly apply to clinical RLTs and play a crucial role in determining the efficacy and toxicity profile of different radiopharmaceutical agents. Personalized dosimetry is a powerful tool that aids in estimating patient-specific absorbed doses in both tumors and normal organs. Dosimetry in RLT is an area of active investigation, as our current understanding of the relationship between absorbed dose and tissue damage is primarily derived from external-beam radiation therapy. Further research is necessary to comprehensively comprehend this relationship in the context of RLTs. In the present review, we present a thorough examination of the involvement of Lu/Ac radioisotopes in the induction of direct and indirect DNA damage, as well as their influence on the initiation of DNA repair mechanisms in cancer cells of neuroendocrine tumors and metastatic prostate cancer. Current data indicate that high-energy α-emitter radioisotopes can directly impact DNA structure by causing ionization, leading to the formation of ionized atoms or molecules. This ionization process predominantly leads to the formation of irreparable and intricate double-strand breaks (DSBs). On the other hand, the majority of DNA damage caused by β-emitter radioisotopes is indirect, as it involves the production of free radicals and subsequent chemical reactions. Beta particles themselves can also physically interact with the DNA molecule, resulting in single-strand breaks (SSBs) and potentially reversible DSBs.

: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience significantly reduced functional capacity due to myocardial involvement. Cardiopulmonary exercise testing (CPET) is the gold standard to quantify functional capacity, and Tc-DPD scintigraphy and SPECT/CT have proven to be highly effective tools for diagnostic and disease monitoring. We aimed to investigate the complementary role and correlation between both methods, focusing on their combined potential as a strong prognostic framework for monitoring disease progression and evaluating treatment efficacy. : A total of 44 patients with diagnosed ATTR-CM, who underwent Tc-DPD scintigraphy and SPECT/CT imaging as well as CPET, were included. All patients were divided into two groups based on the median DPD retention index (low DPD uptake: ≤5.0, n = 22; high DPD uptake: >5.0, n = 22). : The mean age was 78 years, with 82% of participants being male. Significant correlations were observed between peak VO and DPD retention index (r = -0.355, = 0.018) as well as between peak VO at anaerobic threshold with DPD retention index (r = -0.391, = 0.009). Interestingly, there was no strong correlation between VE/VCO slope and the retention index. A strong association was identified between cardiac biomarkers and peak VO, specifically for NT-proBNP (r = -0.530, < 0.001) and Troponin T (r = -0.431, < 0.001). : In ATTR-CM, significant correlations were observed between key CPET parameters and quantitative cardiac DPD uptake, which further reflects on disease severity and functional impairment. Our findings highlight the utility of integrating CPET and SPECT/CT for comprehensive patient assessment in ATTR-CM.

[Tc]Tc-GSA, an albumin-based glycoprotein, is routinely used in Japan to measure the asialoglycoprotein receptor (ASGR) density via single photon emission tomography. Here we describe the development of Ga-labeled peptide-based alternatives. Peptides were assembled on a solid support using a fragment coupling strategy. Glycosylation was carried out via a click chemistry approach resulting in a set of three peptides with increasing amounts of d-galactose ( = 3, 6, and 9) as well as one glycopeptide bearing nine -acetylgalactosamine residues. Ga-labeling of all compounds could be achieved in high radiochemical yields (>95%). Radiotracers exhibited high hydrophilicity, good metabolic stability in human serum and protein binding between 12 and 22%. The IC values improved in the series tri-, hexa-, and nonamer with an IC of 50 ± 30 pM for the latter one. In analogy, the biodistribution studies revealed increased liver uptake in the series of [Ga]Ga- (9.4 ± 2.0% ID/g, 30 min p.i.), [Ga]Ga- (55.5 ± 7.4% ID/g, 30 min p.i.), and [Ga]Ga- (79.6 ± 8.0% ID/g, 30 min p.i.). [Ga]Ga-NODAGA-GalNAc-NonaLysan reached comparable liver uptake to [Ga]Ga-, but showed higher accumulation in nontarget organs. The impressive imaging properties of [Ga]Ga- were also confirmed by the PET/MR imaging studies in mice. Hence, [Ga]Ga- represents a new PET radiopharmaceutical with even better imaging properties than [Tc]Tc-GSA.

Dopamine transporter imaging is routinely used in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) diagnosis. While [C]CFT PET is prevalent in Asia with a large APS database, Europe relies on [I]FP-CIT SPECT with limited APS data. Our aim was to develop a deep learning-based method to convert [C]CFT PET images to [I]FP-CIT SPECT images, facilitating multicenter studies and overcoming data scarcity to promote Artificial Intelligence (AI) advancements.

To evaluate right ventricular (RV) uptake measured by quantitative [Tc]Tc-DPD SPECT/CT to investigate its role in predicting and evaluating prognosis and therapeutic outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CA).

Clinical parameters measured from gated single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) have value in predicting cardiac resynchronization therapy (CRT) patient outcomes, but still show limitations. The purpose of this study is to combine clinical variables, features from electrocardiogram (ECG), and parameters from assessment of cardiac function with polar maps from gated SPECT MPI through deep learning (DL) to predict CRT response. A total of 218 patients who underwent rest-gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6-month follow-up. A DL model was constructed by combining a pre-trained VGG16 model and a multilayer perceptron. Two modalities of data were input to the model: polar map images from SPECT MPI and tabular data from clinical features, ECG parameters, and SPECT-MPI-derived parameters. Gradient-weighted class activation mapping (Grad-CAM) was applied to the VGG16 model to provide explainability for the polar maps. For comparison, four machine learning (ML) models were trained using only the tabular features. Modeling was performed on 218 patients who underwent CRT implantation with a response rate of 55.5% (n = 121). The DL model demonstrated average AUC (0.83), accuracy (0.73), sensitivity (0.76), and specificity (0.69) surpassing ML models and guideline criteria. Guideline recommendations achieved accuracy (0.53), sensitivity (0.75), and specificity (0.26). The DL model trended towards improvement over the ML models, showcasing the additional predictive benefit of utilizing SPECT MPI polar maps. Incorporating additional patient data directly in the form of medical imagery can improve CRT response prediction.

Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA.

The pathophysiological hallmark of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is the deposition of amyloid within the myocardium.

Despite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-D (AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina.

Recovery of cardiovascular diagnostic testing in Italy after the coronavirus disease-2019 (COVID-19) pandemic has not been quantified. The study aims to describe cardiac diagnostic procedure volumes, centres practice and protocols, and staff members' well-being 1 year after COVID-19 outbreak in Italy.

Glioblastoma (GBM), the most common malignant brain tumor, is associated with devastating outcomes. IPAX-1 was a multicenter, open-label, single-arm phase I study to evaluate carrier-added 4--[I]iodo-phenylalanine ([I]IPA) plus external radiation therapy (XRT) in recurrent GBM.

Since its inception in 2012, the Nuclear Medicine Global Initiative (NMGI) of the Society of Nuclear Medicine and Molecular Imaging has played an important role in addressing significant challenges in the field of nuclear medicine and molecular imaging. The first 3 projects were dedicated to standardizing pediatric nuclear medicine practices, addressing the global challenges of radionuclide access and availability, and assessing the educational and training initiatives on theranostics across the globe. These efforts aimed to advance human health, foster worldwide educational collaboration, and standardize procedural guidelines to enhance quality and safety in nuclear medicine practice. In its latest project, NMGI aimed to develop a unified nomenclature for systemic radionuclide therapy in nuclear medicine, addressing the diverse terminology currently used. An online survey was distributed to NMGI member organizations, drawing participation from various geographical locations and disciplines. The survey anonymously collected responses from physicians, physicists, scientists, radiopharmacists, radiopharmaceutical scientists, dosimetrists, technologists, and nurse managers, totaling 240 responses from 30 countries. Findings revealed a prevailing use of the term targeted radionuclide therapy for radionuclide therapy, with 52% of respondents expressing a preference for this term. In contrast, approximately 37% favored "radiopharmaceutical therapy," whereas 11% favored "molecular radionuclide therapy." Other key terms under the umbrella of targeted radionuclide therapy were also discussed to achieve a consensus on terminology. NMGI efforts to standardize terminology in this dynamic and fluid field should improve communication within the field, better reflect the technology used, enable comparison of results, and ultimately lead to improved patient outcomes.

Despite the potential of dosimetry in optimizing personalized radiopharmaceutical therapy (RPT), its limited clinical implementation impedes the development of simplified protocols for routine adoption. However, simplifications may introduce errors in dosimetry, prompting questions about their impact on clinical practice.

Radiolabelled minigastrin (MG) analogues targeting the cholecystokinin-2 receptor (CCK2R) have proven to be a promising approach for peptide receptor radionuclide therapy (PRRT). In this study, we report on the radiopharmaceutical development and standardization of the preparation of [Lu]Lu-DOTA-MGS5 using an automated synthesis module. Furthermore, we present the preclinical tests required to move forward towards a first therapeutic clinical trial as well as preliminary clinical dosimetry data.

First isolated by Brazeau et al. in 1972, somatostatin (SST) is a neuropeptide known for regulating various signaling pathways through its specific cell surface receptors. Somatostatin receptors (SSTRs) comprise a family of five G protein-coupled receptors that are widely distributed across the human body and are expressed by various tumor types. The growing understanding of their clinical potential led to the introduction of both cold and radiolabeled somatostatin analogs (SSAs), which have revolutionized the management of several cancers, especially neuroendocrine tumors. As a direct consequence, advances in peptide receptor radionuclide therapy (PRRT) over the last 30 years led to the approval of Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs). Theoretically, any cancer patients whose tumors express SSTR, as demonstrated in vivo through SSTR-based molecular imaging, could be candidates for PRRT, especially those with limited treatment options. However, evidence on the efficacy of PRRT in non-GEPNET SSTR-expressing tumors is limited, and mainly derived from small retrospective studies. Given the limited therapeutic options for advanced/metastatic patients, there is a clear need for randomized trials to formally approve PRRT with SSAs for patients who may benefit from this treatment, particularly in certain types of neuroendocrine neoplasms such as lung carcinoids, paragangliomas, and meningiomas, where high rates of disease control (up to 80%) can be achieved. In addition, emerging evidence supports the potential of combination therapies, alpha emitters, and non-SSTR-based radionuclide therapy in tumors beyond GEPNET. This review aims to provide a comprehensive overview of PRRT's role in cancers beyond GEPNET, exploring new possibilities and future directions for most SSTR highly expressing tumors.

High-grade meningiomas have high recurrence rates and limited prognosis. Radioligand therapies are approved in extracranial malignancies, but their value in brain tumours including meningiomas is unclear, as data on target expression is scarce.

Theranostics is a new treatment modality integrating molecular imaging with targeted radionuclide therapy. Theranostic agents have received regulatory approval for some systemic cancers and have therapeutic potential in neuro-oncology. As clinical trials are developed to evaluate the efficacy of theranostic agents in brain tumors, specific considerations will have to be considered, taking into account lessons learned from previous studies examining other treatment modalities in neuro-oncology. These include the need for molecular imaging or surgical window-of-opportunity studies to confirm adequate passage across the blood-brain barrier, optimize eligibility criteria, and selection of the most appropriate response criteria and endpoints to address issues such as pseudoprogression. This review will discuss some of the issues that should be considered when designing clinical trials for theranostic agents.

 High-dose epidermal radionuclide therapy using a nonsealed Re (Rhenium) resin is an alternative treatment option for nonmelanoma skin cancer. In this case study, we present the possible use of this therapy in a patient with multiple actinic keratosis (AK), which is a precancer of the skin.  A 55-year-old male was presented in our department with multiple AK, located on the cheek, temporal, and frontal area, with 1, 1, 2.1, and 2.5 cm surface. Applied activity was 80, 80, 167, and 168 MBq Re with a target absorbed dose for each lesion 35 Gy at 1 mm. The treatment was well tolerated.  At 17 months' follow-up, all treated area showed complete remission. There were no side effects, except mild focal hypopigmentation.  This case demonstrates the high potential of epidermal radionuclide therapy with a nonsealed Re as a noninvasive, effective, and well-tolerated therapy option for patients with multiple AK, when surgery is difficult to perform or not recommended of other reasons.

Atherosclerosis and its sequels, such as coronary artery disease and cerebrovascular stroke, still represent global health burdens. The pathogenesis of atherosclerosis consists of growing calcified plaques in the arterial wall and is accompanied by inflammatory processes, which are not entirely understood. This study aims to evaluate the effect of peptide receptor radionuclide therapy (PRRT) using Y- and Lu-DOTATATE on atherosclerotic plaque inflammation. : Atherosclerotic plaques in 57 cancer patients receiving PRRT using Y- and Lu-DOTATATE were longitudinally monitored by Ga-DOTATATE PET/CT. The target-to-background ratio (TBR) and overall vessel uptake (OVU) were measured in eight distinct arterial regions (ascending aorta, aortic arch, descending aorta, abdominal aorta, both iliac arteries, and both carotid arteries) to monitor calcified plaques. PET/CT analysis shows a positive correlation between calcified plaque scores and the Ga-DOTATATE overall vessel uptake (OVU) in cancer patients. After PRRT, an initially high OVU was observed to decrease in the therapy group compared to the control group. An excellent correlation could be shown for each target-to-background ratio (TBR) to the OVU, especially the ascending aorta. The ascending aorta could present a future reference for estimating generalized atherosclerotic inflammatory processes. PRRT might represent a therapeutic approach to modulating atherosclerotic plaques.

This systematic review aims to examine the safety and efficacy of fibroblast activation protein inhibitor (FAPI) radioligand therapy (RLT) for various epithelial neoplasms. PubMed, Web of Science, and Scopus databases were searched up to Jan 4, 2025, for studies involving FAPI RLT in various cancers. Data extraction focused on exploring safety and efficacy of FAPI RLT. Overall, 27 studies involving a total of 144 patients who received FAPI RLT were included in this systematic review. [Lu]Lu-FAPI was employed in 21 studies, with 225 cycles administered to 95 patients at a median dose of 6.8 GBq/cycle. Six non-randomized clinical investigations using [Lu]Lu-FAPI reported disease control rates ranging from 18.2% to 83.3%. Only three studies documented a cumulative total of six patients who experienced grade 3 or 4 toxicity post [Lu]Lu-FAPI RLT. Of 16 case reports utilizing [Lu]Lu-FAPI, nine achieved disease control across various cancer types, with no reported adverse events. Four studies employed [Y]Y-FAPI, totaling 103 cycles in 42 patients at a median dose of 6.7 GBq/cycle. Three non-randomized clinical investigations reported disease control rates of 50% to 82%, with two studies documenting eight high-grade toxicity events. Furthermore, a successful administration of [Y]Y-FAPI was employed in a single reported case involving multiple primary neoplasms with no reported adverse events. However, the patient did not achieve disease control post [Y]Y-FAPI. A cohort study utilized 53 [Bi]Bi-FAPI-46 injections following a fractionated dose regimen in six cancer patients, achieving a 33.3% disease control rate without reported adverse events. One case report described dual radionuclide therapy using two cycles with a cumulative 20 GBq [Sm]Sm-FAPI and a third 8 GBq [Y]Y-FAPI cycle in a lung cancer patient, resulting in stable disease for eight months. FAPI RLT is a promising and safe therapeutic agent in oncology, with potential benefits achieved on short-term basis. However, its long-term efficacy and safety require further research with larger, controlled studies, considering the currently observed variations in patient populations, cancer types, and methodologies within reviewed studies.

Radioligand therapy (RLT) has garnered significant attention due to the recent emergence of innovative and effective theranostic agents, which showed promising therapeutic and prognostic results in various cancers. Moreover, understanding the interaction between different types of radiation and biological tissues is essential for optimizing therapeutic interventions These concepts directly apply to clinical RLTs and play a crucial role in determining the efficacy and toxicity profile of different radiopharmaceutical agents. Personalized dosimetry is a powerful tool that aids in estimating patient-specific absorbed doses in both tumors and normal organs. Dosimetry in RLT is an area of active investigation, as our current understanding of the relationship between absorbed dose and tissue damage is primarily derived from external-beam radiation therapy. Further research is necessary to comprehensively comprehend this relationship in the context of RLTs. In the present review, we present a thorough examination of the involvement of Lu/Ac radioisotopes in the induction of direct and indirect DNA damage, as well as their influence on the initiation of DNA repair mechanisms in cancer cells of neuroendocrine tumors and metastatic prostate cancer. Current data indicate that high-energy α-emitter radioisotopes can directly impact DNA structure by causing ionization, leading to the formation of ionized atoms or molecules. This ionization process predominantly leads to the formation of irreparable and intricate double-strand breaks (DSBs). On the other hand, the majority of DNA damage caused by β-emitter radioisotopes is indirect, as it involves the production of free radicals and subsequent chemical reactions. Beta particles themselves can also physically interact with the DNA molecule, resulting in single-strand breaks (SSBs) and potentially reversible DSBs.