Publikationen

This study aimed to determine the optimized scan time and injected activity regimen for clinical Ga DOTATATE PET/CT in neuroendocrine tumor imaging through an experimental approach without using machine learning techniques.A NEMA PET body phantom was used with Ga- to simulate a 9:1 sphere-to-background ratio. PET data were acquired on a high-sensitivity scanner at various scan times (15-300 s/bed). For each scan time, coefficient of variation (COV) and contrast-to-noise ratio (CNR) were calculated. The minimum scan time (T) needed to meet the Rose Criterion (CNR > 5) for the smallest sphere was identified. This T was then applied to patient scans with neuroendocrine tumors (originally acquired at 120 s/bed) to evaluate image quality and determine an optimized activity regimen for clinical Ga-DOTATATE PET imaging.Phantom experiments showed that a COV of 20% is the highest acceptable noise level for detecting the smallest lesions, corresponding to a minimum scan time of about 1 minute per bed position. Patient image analysis confirmed that all tumors visible at routine scan times were still detectable at this minimum duration. This supports the use of a lower activity regimen (~1 MBq/kg), which can reduce patient radiation exposure compared to the standard 1.85 MBq/kg protocol.This work demonstrated that scan time and activity for Ga-DOTATATE NET imaging can be significantly minimized without compromising image interpretation and quantification.

Clinically accurate detection of prostate cancer (PCa) metastases is crucial for management of high-risk PCa patients scheduled for radical prostatectomy. We determine the safety and diagnostic accuracy of pre-operative Ga-PSMA-11 PET/CT imaging in newly diagnosed high-risk PCa and assess its impact on patient management.

To investigate the clinical potential of O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET) PET imaging in the management of circumscribed astrocytic gliomas (CAG), a rare glioma subtype with limited imaging data.

High-sensitivity, total-body (TB) positron emission tomography (PET) and computed tomography (CT) imaging systems enable substantial reduction of injected radioactivity without compromising image quality. Synthetic CT-like attenuation maps can be generated from PET data via deep learning (DL) to further minimise subject radiation exposure. We explored combining TB-PET with DL-derived attenuation maps to minimise effective dose in healthy subjects undergoing TB-PET/CT imaging with [F]Fluorodeoxyglucose ([F]FDG).

Complete and minimally invasive cancer surgery remains challenging. Targeting the fibroblast activation protein (FAP) offers valuable opportunities for surgical planning, intraoperative guidance and improved resection outcomes. Herein, we developed the first dimeric, dual-modality FAP-targeted imaging agents and investigated the influence of different near-infrared cyanine-7 dyes on their final properties.

To analyze the association of pathologic-complete-response (PCR) and survival after neoadjuvant concurrent chemo-radiotherapy, we evaluated a large cohort of patients with potentially resectable stage IIIA-IIIC non-small cell lung cancer (NSCLC) treated with a trimodality approach.

An integrated model combining clinical variables, radiomic features, and deep learning was developed to predict EGFR mutation status in patients with lung adenocarcinoma based on pretreatment F-FDG PET/CT imaging.

Systematic transrectal ultrasound-guided biopsy lacks accuracy in the primary diagnosis of prostate cancer (PCa) and causes side effects. We investigated prostate-specific membrane antigen (PSMA)-targeted PET/MRI as a less-invasive alternative for biopsy guidance and risk assessment. The RAPID study was a randomized, controlled, single-center, open-label phase 3 trial comparing the diagnostic efficacy of Ga-PSMA-11 PET/MRI with systematic transrectal ultrasound-guided prostate biopsy. In total, 220 men with suspected PCa were randomized to either a standard (random 12-core biopsy; RB) group or an image-guided biopsy (IGB) group. Biopsy, prostatectomy histology, and follow-up visits served as references. PET/MRI prospectively predicted 91 of 113 histologically verified tumors, corresponding to a sensitivity of 80.5% and a positive predictive value of 84.3%. Among tumors characterized as ISUP GG of 3 or greater ( = 60), PSMA PET/MRI prospectively detected 95% ( = 57). The IGB group demonstrated slightly higher sensitivity, specificity, positive predictive value, and negative predictive value compared with the RB group (79.3%, 94.7%, 85.2%, 92.2% vs. 74.2%, 88.0%, 71.9%, 89.2%). Seventy-nine patients were eligible for a direct IGB and RB subanalysis, with IGB detecting 15 additional cases. PET/MRI showed high specificity (94%) and negative prediction (86%) for tumor aggressiveness. In a median follow-up period of 3 y, an aggressive course of disease was detected in 25 of 199 patients. RB correlation identified 24 patients with an ISUP GG of 3 or greater with aggressive disease development during follow-up, compared with 23 patients identified by PET/MRI. Negative prediction of both methods was comparably high at 99%; however, PET/MRI overestimated fewer patients (21) as aggressive compared with RB (34). PSMA-targeted PET/MRI-guided biopsy is a reliable, less invasive method for detecting and characterizing PCa in a cohort with moderately increased PSA values, potentially reducing unnecessary biopsies and provides a reliable prognosis of the course of disease. These results support the integration of modern imaging techniques into clinical practice to improve the treatment of PCa.

Over the past years, we have developed GATE version 10, a major reimplementation of the long-standing Geant4-based Monte Carlo application for particle and radiation transport simulation in medical physics. This release introduces many new features and significant improvements, most notably a Python-based user interface replacing the legacy static input files. The new functionality of GATE version 10 is described in the part 1 companion paper (Sarrut et al., 2025).The development brought significant challenges. In this paper, we present the solutions that we have developed to overcome these challenges. In particular, we present a modular design that robustly manages the core components of a simulation: particle sources, geometry, physics processes, and data acquisition. The architecture consists of parts written in C++ and Python, which needed to be coupled. We explain how this framework allows for the precise, time-aware generation of primary particles, a critical requirement for accurately modeling positron emission tomography (PET), radionuclide therapies, or prompt-gamma timing systems. We present how GATE 10 handles complex Geant4 physics settings while exposing a simple interface to the user. Furthermore, we describe the methodological solutions that facilitate the seamless integration of advanced physics models and variance reduction techniques. The architecture supports sophisticated scoring of physical quantities (such as Linear Energy Transfer and Relative Biological Effectiveness) and is designed for multithreaded execution. The new user interface allows researchers to script complex simulation workflows and directly couple external tools, such as artificial intelligence models for source generation or detector response. By detailing these architectural innovations, we demonstrate how GATE 10 provides a more powerful and flexible tool for research and innovation in medical physics.This paper is not intended to be a developer guide. Its purpose is to share with the research community in-depth explanations of our development effort that made the new GATE 10 possible.

: While TSH suppression is essential in patients with differentiated thyroid cancer (DTC) to reduce the risk of recurrence, it has also been linked to side effects, particularly a reduction in bone mineral density that may contribute to osteoporosis. However, previous studies investigating this association have yielded inconsistent results. This study aimed to evaluate bone density using Hounsfield units from PET/CT scans in a longitudinal analysis including both sexes. : Patients with DTC under continuous TSH suppression who underwent two PET/CT scans were included. Hounsfield units were measured for each lumbar vertebra (L1-L5) in the CT by placing an elliptical region of interest (ROI) in the center of the vertebra, avoiding hyperdense edges. Laboratory parameters were also collected. : A total of 50 patients were included in the study (25 male, 25 female), with a mean age of 57.2 (±15.3) years at the time of the first scan. The mean duration of TSH suppression before the first scan was 3.7 ± 3.9 years, and the mean interval between both scans was 4.4 ± 4.0 years. At the follow-up scan, bone density was significantly lower compared with baseline for all lumbar vertebrae (L1-L5 combined and individually) (all < 0.05). Subgroup analysis revealed a significant decline in women at L1, L2, L4, and L5 and for overall lumbar bone density, while men showed nonsignificant trends. : Our study suggests a sustained reduction in vertebral bone density during TSH suppression. The results support routine monitoring in both sexes, risk stratification by age and duration of suppression, and, when oncologically appropriate, consideration of lower suppression intensity or initiation of bone-protective therapy in high-risk patients.

Left ventricular (LV) myocardial uptake of Technetium-labeled tracers is assessed to diagnose transthyretin amyloid cardiomyopathy (ATTR-CM). The degree of uptake is visually graded using planar images utilising the Perugini score. Today, non-invasive diagnosis of ATTR-CM is broadly established in practice; however, in patients with mild tracer uptake (Perugini grade 1), no definite diagnosis can be made without endomyocardial biopsy.

Targeting dynamic inflammatory-fibrotic pathways post-myocardial infarction (MI) is essential for exploring novel biomarkers to improve healing and attenuate adverse left ventricular (LV) remodeling. This study aimed to investigate the spatiotemporal dynamic pattern of immune inflammation and fibroblast activation and to map the proteomic profile of different regions over time after acute MI (AMI).

Complete and minimally invasive cancer surgery remains challenging. Targeting the fibroblast activation protein (FAP) offers valuable opportunities for surgical planning, intraoperative guidance and improved resection outcomes. Herein, we developed the first dimeric, dual-modality FAP-targeted imaging agents and investigated the influence of different near-infrared cyanine-7 dyes on their final properties.

Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive, underdiagnosed disease with high morbidity and mortality. While disease-modifying therapies (DMTs) slow progression, early treatment response markers remain scarce. This study assessed AI-quantified thoracic [Tc]Tc-DPD SPECT/CT markers as potential non-invasive biomarkers for monitoring therapeutic efficacy.

Current machine learning-based (ML) models usually attempt to utilize all available patient data to predict patient outcomes while ignoring the associated cost and time for data acquisition. The purpose of this study is to create a multi-stage ML model to predict cardiac resynchronization therapy (CRT) response for heart failure (HF) patients. This model exploits uncertainty quantification to recommend additional collection of single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) variables if baseline clinical variables and features from electrocardiogram (ECG) are not sufficient. Two hundred eighteen 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 ± 1 month follow-up. A multi-stage ML model was created by combining two ensemble models: Ensemble 1 was trained with clinical variables and ECG; Ensemble 2 included Ensemble 1 plus SPECT MPI features. Uncertainty quantification from Ensemble 1 allowed for multi-stage decision-making to determine if the acquisition of SPECT data for a patient is necessary. The performance of the multi-stage model was compared with that of Ensemble models 1 and 2. The response rate for CRT was 55.5% (n = 121) with overall male gender 61.0% (n = 133), an average age of 62.0 ± 11.8, and LVEF of 27.7 ± 11.0. The multi-stage model performed similarly to Ensemble 2 (which utilized the additional SPECT data) with AUC of 0.75 vs. 0.77, accuracy of 0.71 vs. 0.69, sensitivity of 0.70 vs. 0.72, and specificity 0.72 vs. 0.65, respectively. However, the multi-stage model only required SPECT MPI data for 52.7% of the patients across all folds. By using rule-based logic stemming from uncertainty quantification, the multi-stage model was able to reduce the need for additional SPECT MPI data acquisition without significantly sacrificing performance.

Hippocampal injury is linked to cognitive impairment and cardiac events in patients with heart failure with reduced ejection fraction. However, the predictive value of hippocampal metabolic activity (HMA) for sudden cardiac death (SCD) and the underlying mechanisms remain unclear. This study aimed to evaluate the independent and incremental predictive value of HMA over myocardial scar for SCD-related events in patients with heart failure with reduced ejection fraction and to explore the potential mechanism.

: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [Tc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. : CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed by Western blotting. : studies showed similar target-specific binding and internalization of [In]In-RM2 and [Tc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, imaging showed negligible tumor uptake in xenografts of the transduced cell lines. analysis indicated a loss of the respective biomarkers in the xenografts. : Although the technical feasibility of a dual-tracer SPECT imaging approach using In and Tc has been demonstrated, the potential of [Tc]Tc-PSMA-I&S and [In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The / experiments indicated that results from an model may not necessarily be successfully transferred to an setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches.

: 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.

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.

Continuation of effective and well-tolerated systemic treatment is often performed in care for metastatic castration-resistant prostate cancer. Likewise, continued administration of [Lu]Lu-PSMA radiopharmaceutical therapy beyond the approved number of cycles holds promising potential to enhance therapeutic efficacy. Rechallenge therapy involves readministration of [Lu]Lu-PSMA cycles after a break, whereas extended therapy continues treatment beyond the standard 6 cycles without interruption. Both approaches aim to improve disease control and prolong survival in patients with metastatic castration-resistant prostate cancer. However, practices vary: some clinicians continue treatment in patients with early favorable responses, whereas others recommend pausing therapy after significant prostate-specific antigen declines, even after a few cycles. In this narrative review, we show that safety profiles for continued [Lu]Lu-PSMA radiopharmaceutical therapy are generally favorable, and most adverse events are mild to moderate in severity. Hematotoxicity, particularly anemia and thrombocytopenia, is the most significant concern, with few patients experiencing high-grade adverse events. In addition, cumulative irradiation, particularly during extended therapy, necessitates careful monitoring of hematologic and renal function. Biochemical responses to rechallenge and extended [Lu]Lu-PSMA therapy are promising, with at least 50% reductions in prostate-specific antigen levels observed in a significant proportion of highly selected patients. Moreover, survival outcomes are encouraging, showing the extension of overall and progression-free survival beyond the known data for standard therapy. Despite these advances, challenges remain in optimizing patient selection, managing cumulative toxicities, and harmonizing treatment protocols. In addition, variability in trial designs, influenced by international regulatory differences, limits the current evidence and necessitates consideration of each treatment approach within its regulatory context. Prospective studies are needed to refine therapeutic strategies, implement consistent clinical and imaging response criteria, and identify predictive biomarkers to improve both efficacy and safety.

Recent data demonstrate that one possibility for increasing Peptide Receptor Radionuclide Therapy (PRRT) results lies in the combination of PRRT with chemotherapy. This study aimed to evaluate response and outcome in [F]FDG-positive metastatic neuroendocrine tumor (mNET) patients treated with PRRT alone or in combination with temozolomide (TEM) plus/minus capecitabine (CAP).

Radiopharmaceutical therapy (RPT) is entering a new era of personalization, driven by advances in molecular imaging, radiopharmaceutical development, and a growing body of clinical evidence linking absorbed dose to treatment outcomes. Although external-beam radiotherapy has long integrated dosimetry into standard practice, RPT historically relied on fixed radiopharmaceutical activities and absorbed dose-effect relationships adapted from external-beam radiotherapy, often without accounting for the unique pharmacokinetics, absorbed dose rate dynamics, and biologic responses of systemically administered radiopharmaceuticals. As RPT expands into earlier disease stages, at which patients have longer life expectancies and better performance status, the role of dosimetry in optimizing treatment is becoming increasingly evident. However, despite growing recognition of its benefits, the implementation of dosimetry in clinical practice remains limited, partly because of a self-reinforcing cycle in which the lack of routine dosimetry limits clinical evidence, which in turn hinders its broader adoption. Breaking this cycle is essential to advancing RPT and ensuring that evaluation of dosimetry is based on clinical merit rather than logistic constraints. This article examines the current landscape of RPT dosimetry, highlighting key challenges and opportunities from a European perspective and aiming to foster a more factual and constructive discussion on the topic. We discuss the fundamental differences between dosimetry-driven treatment planning and posttherapy absorbed dose verification, emphasizing the latter as a practical entry point for clinical adoption. We underscore the need for harmonized standards, improved imaging resolution, and tailored absorbed dose-effect relationships that reflect the heterogeneity of RPT delivery and the complexity of tumor and organ responses. The paper also addresses regulatory, infrastructural, and resource barriers to RPT dosimetry implementation and highlights ongoing European initiatives to strengthen frameworks, enhance stakeholder collaboration, and integrate absorbed dose biomarkers into authorization processes and clinical decision-making. By rethinking dosimetry and promoting standardized, evidence-based approaches, the field can advance beyond fixed-activity protocols toward truly individualized RPT. However, achieving clinically feasible integration of dosimetry into routine practice requires structured efforts to generate high-quality clinical evidence and improve accessibility. Ultimately, reliable, patient-centered dosimetry has the potential to enhance therapeutic efficacy, manage toxicity more effectively, and support the long-term evolution of RPT as a cornerstone of precision oncology.

There are no established treatment options for patients with meningioma recurring after surgery and radiotherapy. Somatostatin receptor type 2 (SSTR2) is highly expressed in meningiomas, and SSTR2-targeting radionuclide therapy with [Lu]Lu-DOTATATE has shown potential activity in the treatment of meningioma in uncontrolled and small studies. EORTC-2334-BTG (LUMEN-1, NCT06326190) is a randomized, multicenter, phase II trial in patients with recurrent World Health Organization (WHO) grade 1, 2, or 3 meningioma. In total, 136 patients will be randomized in a 2:1 ratio to [Lu]Lu-DOTATATE (≤4 doses of 7.4 GBq given every 4 wk) or local standard of care (hydroxyurea, bevacizumab, sunitinib, octreotide, everolimus, or observation). The main eligibility criteria include age 18 y or older; neuropathologically confirmed meningioma of WHO grade 1, 2, or 3; WHO performance score of 0-2; measurable disease on MRI (≥10 × 10 mm); radiologically documented progression of any existing tumor (growth > 25% or new lesions) or appearance of new lesions within the last 2 y; SSTR positivity by PET imaging (SUV > 2.3); at least 1 prior surgery and at least 1 line of radiotherapy; and no prior systemic therapy. The primary efficacy endpoint is locally assessed progression-free survival according to Response Assessment in Neuro-Oncology MRI meningioma criteria, and secondary endpoints include radiologic response rate, overall survival, safety, health-related quality of life, and neurologic function. The trial protocol includes a comprehensive exploratory translational research program with dosimetry and imaging-based and tissue-based investigations. LUMEN-1 was activated in March 2025 and will enroll patients in 35 sites in 10 countries across Europe, with primary endpoint collection planned after 2 y and study completion after 5 y. To our knowledge, EORTC-2334-BTG (LUMEN-1, NCT06326190) is the first prospective randomized trial investigating the efficacy of [Lu]Lu-DOTATATE in patients with recurrent meningioma.

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.

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.

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.

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.