Publikationen

Sarcoidosis is a multisystemic granulomatous disease with highly variable manifestations and outcomes, making clinical management challenging. This study evaluated the prognostic value of biomarkers derived from 18F-FDG PET/CT imaging.

Rhabdomyosarcoma (RMS) of the prostate is a rare tumor in infants. RMS frequently arises in genitourinary tract (~20% of cases), with the embrional subtype being the most common. 1,2 The presenting symptoms are usually not specific, often leading to an extensive diagnostic work-up before identifying RMS. 3,4 Furthermore, there are no biomarkers specific to RMS. We present the case of a 4-month-old boy with postrenal acute kidney injury (AKI). Abdominal ultrasound and magnetic resonance imaging (MRI), followed by ultrasound-guided fine-needle aspiration biopsy and citopathological examination, established the diagnosis of prostatic RMS, which was later staged with 18 F-FDG PET/CT. 5.

Efficient application of immunotherapy necessitates advanced whole-body imaging techniques to monitor sites of immune cell activation. Deoxycytidine kinase (dCK), a key enzyme in the deoxynucleotide salvage pathway, is upregulated in proliferating immune cells and can be targeted by the radiotracers [F]FAC (preclinical) and [F]CFA (clinical), allowing for noninvasive monitoring of immune activation in lymphatic organs via positron emission tomography (PET). In this study, we aimed to assess the efficacy of [F]FAC in detecting immune activation upon immune checkpoint inhibitor therapy (CIT). In vitro, activated T cells and macrophages exhibited significantly higher [F]FAC uptake compared to their naïve counterparts. In vivo, preclinical [F]FAC-PET/MRI revealed a CIT-induced significant increase in [F]FAC uptake in tumor-draining lymph nodes (TDLNs) compared to contralateral lymph nodes, independent of tumor responsiveness. This phenomenon was absent in TDLNs of sham-treated experimental mice. Ex vivo cell sorting further confirmed elevated [F]FAC uptake in T cells from TDLNs following CIT. Consistently, [F]CFA-PET/CT imaging in metastatic melanoma patients demonstrated CIT-induced enhanced regional LN uptake. Together, these findings establish a strong correlation between CIT-induced immune activation and [F]FAC/[F]CFA uptake, underscoring the critical role of TDLNs in cancer immuotherapy. The radiotracers [F]FAC and [F]CFA provide valuable tools for noninvasive monitoring of immune cell activation, potentially unveiling tumor-microenvironment-related resistance mechanisms and advancing the utility of PET imaging in immunotherapy monitoring and patient stratification.

High expression of fibroblast activation protein (FAP) has been associated with inferior survival in several tumor entities. Novel Ga-radiolabeled FAP inhibitors (Ga-FAPIs) allow noninvasive measurement of FAP, which enables the development of prognostic imaging parameters from Ga-FAPI PET/CT. In this study, we compared the prognostic value of Ga-FAPI-46 with F-FDG PET in a cohort of patients with malignant pleural mesothelioma from the FAPI PET observational trial (NCT04571086). Between May 2020 and January 2024, 49 patients with suspected or proven malignant mesothelioma were recruited, 39 of whom were eligible for data analysis. All patients underwent Ga-FAPI-46 and F-FDG PET/CT less than 4 wk apart. Tumor burden was measured semiautomatically, and SUV, SUV, and volumetric parameters (metabolic tumor volume [MTV], total lesion glycolysis/total lesion fibroblast activation, and total tumor SUV) were calculated. The FAP immunoreactive score (IRS) was calculated for tumor samples from a subset of patients ( = 19). Overall survival and progression-free survival were assessed per revised mRECIST (version 1.1). Survival analyses were performed with univariate and multivariate Cox regression and with Kaplan-Meier curves for clinical and imaging parameters, stratified by median. Univariate analysis showed significant survival differences for all volumetric parameters for Ga-FAPI-46 and F-FDG (e.g., Ga-FAPI-46 MTV, 262 d vs. 737 d; = 0.008 vs. F-FDG MTV, 336 d vs. 760 d; = 0.012). Multivariate analysis revealed that MTV was an independent prognostic marker for Ga-FAPI-46 (hazard ratio, 4.44; 95% CI, 1.20-16.43; = 0.025) and F-FDG (hazard ratio, 7.01; 95% CI, 1.29-38.2; = 0.024). Kaplan-Meier analysis of the FAP IRS found that a higher IRS was associated with poorer survival (438 d with an IRS of 0-3 vs. 1,076 d with an IRS of 4-12; = 0.04), but no significant difference was observed in univariate and multivariate analyses. In this modest exploratory cohort of patients with malignant pleural mesothelioma, MTV determined by Ga-FAPI-46 and F-FDG PET/CT had similar prognostic value, and high MTV was an independent risk factor. Ga-FAPI-46 not only complements a diagnostic work-up but also provides prognostic value and could offer alternative theranostic strategies for these patients.

In adults with classic Hodgkin lymphoma (cHL), metabolic tumour volume (MTV) is valuable for risk stratification. This systematic review explored the role of volumetric parameters in children, adolescents and young adults (CAYA) with cHL. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Five databases were searched on 16 October 2024. Eligible studies were peer-reviewed manuscripts, written in English, published since database inception that included patients ≤21 years of age with a diagnosis of cHL treated with chemotherapy ± radiotherapy with a baseline F-Fluorodeoxyglucose (F-FDG) PET/CT scan for MTV quantification. The search strategy identified 3669 studies, of which 35 were eligible for inclusion. Fifteen studies (43%) evaluated a cohort exclusively ≤21 years of age. All eight studies that explored the association of baseline PET parameters with known risk factors identified a significant correlation. Nine of 12 papers (75%) demonstrated a statistically significant correlation with disease response to therapy on PET/CT. Fifteen of 20 papers (75%) demonstrated an independent statistically significant correlation with clinical outcomes. In the CAYAHL population, volumetric PET parameters are valuable for risk stratification despite heterogeneity in results. Future harmonization of the segmentation approach will facilitate incorporation of MTV into clinical practice.

[C]Acetate and [C]acetoacetate are PET radiotracers widely used to assess oxidative metabolism and ketone body utilization, respectively. This study aimed to establish robust, high-yield syntheses of both tracers using a GE TRACERlab FX2 C module, with an emphasis on improving radiochemical purity (RCP), radiochemical yield (RCY), optimizing operational parameters, and developing accurate quality control methods. [C]Acetate was synthesized via Grignard carboxylation using [C]CO and purified with a cartridge-based system. [C]Acetoacetate was produced via in-loop [C]CO carboxylation of a lithium enolate precursor, followed by semi-preparative reversed-phase HPLC purification. Quality control was performed by reported ion-exchange chromatography (IEX-HPLC) and novel reversed-phase HPLC (RP-HPLC). A systematic literature review was conducted to evaluate prior quality control methods for [C]acetoacetate.

Cardiovascular disease (CVD), driven primarily by atherosclerosis, is a major cause of morbidity and mortality among cancer patients. This study aims to evaluate the diagnostic value of [Ga]Ga-FAPI-PET as a novel molecular imaging tool for atherosclerosis, compared with established, non-specific [F]FDG. We retrospectively analyzed twenty patients with bladder cancer who underwent [Ga]Ga-FAPI positron-emission tomography/magnetic resonance (PET/MR) and [F]FDG positron emission tomography/computed tomography (PET/CT) at staging. The target-to-background ratio (TBRs) of both tracers were assessed along six arterial segments, and uptake patterns were compared between the two radiotracers. Additionally, associations between the intensity of PET-active lesions and certain CVD risk factors, as well as the intake of acetylsalicylic acid (ASA), were evaluated. [Ga]Ga-FAPI detects significantly more active arterial PET lesions and shows significantly higher uptake than [F]FDG in the per-lesion analysis (TBR: 1.7 ± 0.5 vs. TBR: 1.4 ± 0.2; difference 19%; < 0.001) and in the patient-based analysis (TBR: 1.7 ± 0.4 vs. TBR: 1.4 ± 0.2; difference 19%; = 0.018). Arterial hypertension ( < 0.001), dyslipidemia ( < 0.001), and particularly type 2 diabetes mellitus ( < 0.001; difference 34%), were significantly associated with elevated [Ga]Ga-FAPI expression compared to [F]FDG uptake. ASA therapy was associated with a significant reduction in arterial [Ga]Ga-FAPI expression than [F]FDG ( = 0.02). [Ga]Ga-FAPI-PET imaging, demonstrating superior detection of atherosclerotic activity compared to [F]FDG, might be a promising molecular imaging marker for atherosclerosis.

18F-fluorocholine is a positron emission tomography (PET) tracer earlier found to be a marker of macrophage content in carotid plaques. We aimed to assess the feasibility of 18F-choline PET-MRI to non-invasively localize vulnerable coronary plaques, using optical coherence tomography (OCT) as a reference standard. Patients with recent myocardial infarction who were scheduled for a secondary angiography of a non-culprit vessel underwent 18F-fluorocholine coronary PET-MRI. Subsequently, OCT was performed during the secondary angiography. Maximum target-to-background (TBRmax) values of 18F-fluorocholine uptake were determined in two vessel sections that contained either vulnerable or stable plaques as defined by OCT. The OCT-based definition of a vulnerable plaque was a fibrous cap thickness < 70 µm. To enhance the detectability of coronary plaques using PET, three different motion-correction strategies were used: multigate respiratory gating motion correction (MRG-MOCO), extended MR-based motion correction (eMR-MOCO), and extended MR-based motion correction with ECG gating (eMR-MOCO-ECG). Fifteen patients were included in this study. One patient needed to be excluded due to extravasation of the tracer. In another patient, no region with only a stable plaque could be identified. TBRmax values were as follows for three different reconstructions in vulnerable versus stable plaques: MRG-MOCO: mean TBRmax 1.45 vs. 1.35, = 0.52 ( = 13); eMR-MOCO: mean TBRmax 1.47 vs. 1.27, = 0.26 ( = 11); eMR-MOCO-ECG: mean TBRmax 1.49 vs. 1.26, = 0.21 ( = 11). 18F-fluorocholine uptake in vulnerable atherosclerotic plaques in coronary arteries was not significantly different from uptake in stable plaques, even though advanced motion-correction methods were applied. That may be caused by multiple factors, such as small coronary plaque size, tracer biology, or remaining cardiac motion.

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.

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).

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.

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.

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.

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.

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.