Because of the lack of prognostic biomarkers, most patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed at an advanced stage of the disease, leading to poor overall survival. There is an unmet need to identify biomarkers for the assessment of HNSCC. The goal of this study was to assess C-C chemokine receptor type 2 (CCR2) as a new diagnostic biomarker for HNSCC. Methods: The sensitivity and specificity of the CCR2-targeting radiotracer 64Cu-DOTA-ECL1i for tumor detection was assessed in a mouse oral carcinoma 1 (MOC1) xenograft model and compared with 18F-FDG. The capability of 64Cu-DOTA-ECL1i for monitoring MOC1 tumor treatment response was evaluated for multiple treatment strategies. The CCR2 inhibitor propagermanium was used for targeted therapy in the MOC1 tumor model, followed by 64Cu-DOTA-ECL1i imaging. The translational potential of 64Cu-DOTA-ECL1i for HNSCC imaging was further investigated using patient-derived xenograft models. Proof-of-concept studies were performed using primary tumors and lymph node metastases of 11 patients with HNSCC. Histopathologic analyses of tumors in mice and humans were performed to characterize the expression of CCR2 and associated cell types. Results: 64Cu-DOTA-ECL1i PET imaged MOC1 tumors with high contrast, tracked the increase of tumor volume, and monitored the treatment responses. Propagermanium effectively inhibited MOC1 tumor growth and significantly improved survival. In the patient-derived xenograft model, 64Cu-DOTA-ECL1i accurately identified the tumors and sensitively tracked their progression. In patients with HNSCC, CCR2 PET revealed strong and heterogeneous uptake within primary tumors and metastatic lymph nodes. Tissue analyses demonstrated overexpression of CCR2 on both tumor cells and macrophages. Conclusion: 64Cu-DOTA-ECL1i PET accurately detected the expression of CCR2 in patients with HNSCC. The effectiveness of propagermanium in the inhibition of MOC1 tumor progression indicated its potential for HNSCC therapy.
{"title":"Assessment of CCR2 PET as a Biomarker for Head and Neck Squamous Cell Carcinoma.","authors":"Alexandria Li,Deborah Sultan,Gyu Seong Heo,Lisa Detering,Divangana Lahad,Hannah Luehmann,Xiaohui Zhang,Rajiu Venkatesan,Jennifer Frye,Julie Belmar,Salma Ramadan,Robert Crowder,Ying-Hwey Nai,Joan Tao,Robert Gropler,Richard Laforest,Ryan S Jackson,Rebecca Chernock,Chieh-Yu Lin,Shunqiang Li,Sidharth Puram,Farrokh Dehdashti,Yongjian Liu","doi":"10.2967/jnumed.125.271601","DOIUrl":"https://doi.org/10.2967/jnumed.125.271601","url":null,"abstract":"Because of the lack of prognostic biomarkers, most patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed at an advanced stage of the disease, leading to poor overall survival. There is an unmet need to identify biomarkers for the assessment of HNSCC. The goal of this study was to assess C-C chemokine receptor type 2 (CCR2) as a new diagnostic biomarker for HNSCC. Methods: The sensitivity and specificity of the CCR2-targeting radiotracer 64Cu-DOTA-ECL1i for tumor detection was assessed in a mouse oral carcinoma 1 (MOC1) xenograft model and compared with 18F-FDG. The capability of 64Cu-DOTA-ECL1i for monitoring MOC1 tumor treatment response was evaluated for multiple treatment strategies. The CCR2 inhibitor propagermanium was used for targeted therapy in the MOC1 tumor model, followed by 64Cu-DOTA-ECL1i imaging. The translational potential of 64Cu-DOTA-ECL1i for HNSCC imaging was further investigated using patient-derived xenograft models. Proof-of-concept studies were performed using primary tumors and lymph node metastases of 11 patients with HNSCC. Histopathologic analyses of tumors in mice and humans were performed to characterize the expression of CCR2 and associated cell types. Results: 64Cu-DOTA-ECL1i PET imaged MOC1 tumors with high contrast, tracked the increase of tumor volume, and monitored the treatment responses. Propagermanium effectively inhibited MOC1 tumor growth and significantly improved survival. In the patient-derived xenograft model, 64Cu-DOTA-ECL1i accurately identified the tumors and sensitively tracked their progression. In patients with HNSCC, CCR2 PET revealed strong and heterogeneous uptake within primary tumors and metastatic lymph nodes. Tissue analyses demonstrated overexpression of CCR2 on both tumor cells and macrophages. Conclusion: 64Cu-DOTA-ECL1i PET accurately detected the expression of CCR2 in patients with HNSCC. The effectiveness of propagermanium in the inhibition of MOC1 tumor progression indicated its potential for HNSCC therapy.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
High renal uptake limits the clinical translation of Claudin 18.2 (CLDN18.2) nanobody probes. We aimed to develop and identify a single-domain antibody-based molecular probe to minimize nonspecific renal accumulation while maintaining high tumor affinity and effective uptake. Methods: A CLDN18.2-targeted nanobody, SNA014, was radiolabeled with 68Ga to yield [68Ga]Ga-SNA014. The binding capability of [68Ga]Ga-SNA014 was evaluated in vitro using flow cytometry, immunohistochemistry, and cell-binding assays. The biologic behavior of [68Ga]Ga-SNA014 in vivo was assessed through small-animal PET imaging, biodistribution studies, and blood pharmacokinetic analysis in human gastric adenocarcinoma xenograft models (both wild-type and CLDN18.2-overexpressing). Furthermore, a preliminary clinical evaluation of [68Ga]Ga-SNA014 was conducted in 3 patients with gastric cancer, including whole-body PET/CT imaging and radiation dosimetry analysis. Results: [68Ga]Ga-SNA014 was successfully synthesized with high radiochemical purity (>95%) and excellent stability both in vitro and in vivo. The probe demonstrated strong binding affinity and specificity toward AGSCLDN18.2 cells. Small-animal PET/CT images of AGSCLDN18.2 tumor-bearing mice exhibited high tumor and stomach uptake and low kidney uptake, and pretreatment with succinylated gelatin further reduced kidney retention. Blood clearance revealed a rapid elimination profile, with a half-life of 47.68 ± 1.83 min. In human PET/CT studies, distinct visualization of lesions was achieved up to 0.5 h postinjection. Dosimetry analysis revealed that the effective radiation dose of [68Ga]Ga-SNA014 was lower than that of standard [18F]FDG PET/CT. Conclusion: These findings demonstrated that [68Ga]Ga-SNA014 exhibits high affinity and specificity and excellent targeting performance and safety, enabling precise detection of CLDN18.2-overexpressing tumors.
{"title":"Single-Domain Antibody Probe with Low Renal Uptake for Claudin 18.2-Targeted PET Imaging of Gastric Cancer: Preclinical and Pilot Clinical Evaluations.","authors":"Meng Zheng,Haoqun Ma,Tao Xu,Huiwen Mu,Qingfeng Liu,Kaijie Zhang,Yicong Bian,Hua Zhang,Wei Li,Bin Zhang,Yuanyuan Shan,Xuanhui Peng,Songbing Qin,Yan Wang,Liyan Miao","doi":"10.2967/jnumed.125.271704","DOIUrl":"https://doi.org/10.2967/jnumed.125.271704","url":null,"abstract":"High renal uptake limits the clinical translation of Claudin 18.2 (CLDN18.2) nanobody probes. We aimed to develop and identify a single-domain antibody-based molecular probe to minimize nonspecific renal accumulation while maintaining high tumor affinity and effective uptake. Methods: A CLDN18.2-targeted nanobody, SNA014, was radiolabeled with 68Ga to yield [68Ga]Ga-SNA014. The binding capability of [68Ga]Ga-SNA014 was evaluated in vitro using flow cytometry, immunohistochemistry, and cell-binding assays. The biologic behavior of [68Ga]Ga-SNA014 in vivo was assessed through small-animal PET imaging, biodistribution studies, and blood pharmacokinetic analysis in human gastric adenocarcinoma xenograft models (both wild-type and CLDN18.2-overexpressing). Furthermore, a preliminary clinical evaluation of [68Ga]Ga-SNA014 was conducted in 3 patients with gastric cancer, including whole-body PET/CT imaging and radiation dosimetry analysis. Results: [68Ga]Ga-SNA014 was successfully synthesized with high radiochemical purity (>95%) and excellent stability both in vitro and in vivo. The probe demonstrated strong binding affinity and specificity toward AGSCLDN18.2 cells. Small-animal PET/CT images of AGSCLDN18.2 tumor-bearing mice exhibited high tumor and stomach uptake and low kidney uptake, and pretreatment with succinylated gelatin further reduced kidney retention. Blood clearance revealed a rapid elimination profile, with a half-life of 47.68 ± 1.83 min. In human PET/CT studies, distinct visualization of lesions was achieved up to 0.5 h postinjection. Dosimetry analysis revealed that the effective radiation dose of [68Ga]Ga-SNA014 was lower than that of standard [18F]FDG PET/CT. Conclusion: These findings demonstrated that [68Ga]Ga-SNA014 exhibits high affinity and specificity and excellent targeting performance and safety, enabling precise detection of CLDN18.2-overexpressing tumors.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-12DOI: 10.2967/jnumed.125.271153
Philipp E Hartrampf,Rudolf A Werner,Takahiro Higuchi,Margret Schottelius,Andreas K Buck
{"title":"Is CXCR4 Theranostics in Oncologic, Cardiovascular, and Inflammatory Diseases Really Happening?","authors":"Philipp E Hartrampf,Rudolf A Werner,Takahiro Higuchi,Margret Schottelius,Andreas K Buck","doi":"10.2967/jnumed.125.271153","DOIUrl":"https://doi.org/10.2967/jnumed.125.271153","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.2967/jnumed.125.271605
May Sadik,Måns Larsson,Olof Enqvist,Lars Edenbrandt,Elin Trägårdh
The aim of this study was to evaluate the performance of an artificial intelligence (AI)-based method for automated segmentation of total metabolic tumor volume (TMTV) in 18F-FDG PET/CT scans of patients with lymphoma, using an independent, publicly available benchmark dataset curated and segmented by expert readers in a previously published study. Methods: The AI model, based on a 3-dimensional U-Net architecture implemented in MONAI (the medical open-source network for AI framework), was trained on 1,500 18F-FDG PET/CT scans of patients with lymphoma. It was tested on a benchmark dataset comprising 60 baseline scans (20 each of follicular lymphoma, Hodgkin lymphoma, and diffuse large B-cell lymphoma), each segmented by 3 or 4 nuclear medicine physicians using an SUV threshold of 4. Agreement between AI-derived and benchmark TMTVs was assessed using Bland-Altman analysis, with acceptable deviation defined as within 10% or 10 cm3, consistent with interreader variability reported in the benchmark study. Results: In 50 (83%) of the 60 benchmark cases, AI-derived TMTVs were within 10% or 10 cm3 of the benchmark reference. In 4 of the remaining 10 cases, AI-derived results were within the same margin of at least 1 of the expert readers, indicating partial concordance. Conclusion: The AI-based method achieved high concordance with expert-derived TMTVs in a standardized benchmark setting. The findings demonstrate that the AI model performs comparably to human experts in most cases, even in an externally curated dataset deliberately enriched with challenging cases by its original authors. The AI model's ability to produce accurate, reproducible segmentations without user interaction could significantly reduce manual workload and interreader variability in lymphoma imaging. However, human supervision is required to minimize errors.
{"title":"Validation of an AI Method for Automated Lymphoma Metabolic Tumor Volume Segmentation Using a Public Benchmark PET/CT Dataset.","authors":"May Sadik,Måns Larsson,Olof Enqvist,Lars Edenbrandt,Elin Trägårdh","doi":"10.2967/jnumed.125.271605","DOIUrl":"https://doi.org/10.2967/jnumed.125.271605","url":null,"abstract":"The aim of this study was to evaluate the performance of an artificial intelligence (AI)-based method for automated segmentation of total metabolic tumor volume (TMTV) in 18F-FDG PET/CT scans of patients with lymphoma, using an independent, publicly available benchmark dataset curated and segmented by expert readers in a previously published study. Methods: The AI model, based on a 3-dimensional U-Net architecture implemented in MONAI (the medical open-source network for AI framework), was trained on 1,500 18F-FDG PET/CT scans of patients with lymphoma. It was tested on a benchmark dataset comprising 60 baseline scans (20 each of follicular lymphoma, Hodgkin lymphoma, and diffuse large B-cell lymphoma), each segmented by 3 or 4 nuclear medicine physicians using an SUV threshold of 4. Agreement between AI-derived and benchmark TMTVs was assessed using Bland-Altman analysis, with acceptable deviation defined as within 10% or 10 cm3, consistent with interreader variability reported in the benchmark study. Results: In 50 (83%) of the 60 benchmark cases, AI-derived TMTVs were within 10% or 10 cm3 of the benchmark reference. In 4 of the remaining 10 cases, AI-derived results were within the same margin of at least 1 of the expert readers, indicating partial concordance. Conclusion: The AI-based method achieved high concordance with expert-derived TMTVs in a standardized benchmark setting. The findings demonstrate that the AI model performs comparably to human experts in most cases, even in an externally curated dataset deliberately enriched with challenging cases by its original authors. The AI model's ability to produce accurate, reproducible segmentations without user interaction could significantly reduce manual workload and interreader variability in lymphoma imaging. However, human supervision is required to minimize errors.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"406 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.2967/jnumed.125.271329
Remco J Poelarends,Jorn A van Dalen,Riemer H J A Slart,Brian N Vendel,Walter Noordzij,Joris D van Dijk
{"title":"Toward Reliable Lesion Labeling Standards for AI in Nuclear Medicine.","authors":"Remco J Poelarends,Jorn A van Dalen,Riemer H J A Slart,Brian N Vendel,Walter Noordzij,Joris D van Dijk","doi":"10.2967/jnumed.125.271329","DOIUrl":"https://doi.org/10.2967/jnumed.125.271329","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fever of unknown origin (FUO) presents a significant diagnostic challenge because of its wide range of potential causes. The role of [18F]FDG PET/CT in this complex clinical scenario is not yet fully understood. This multicenter retrospective observational study aimed to investigate the diagnostic value and clinical impact of [18F]FDG PET/CT in patients with FUO and to identify specific factors linked to a positive [18F]FDG PET/CT scan. Methods: We retrospectively included 929 patients from 12 centers who underwent [18F]FDG PET/CT for FUO. The final diagnosis for each patient was established on the basis of laboratory, imaging, histopathologic or pathologic examinations, and at least 6 mo of clinical follow-up data. Final diagnoses were classified into 4 categories: infectious diseases, noninfectious inflammatory diseases, malignancies, and unknown causes (no diagnosis). Moreover, the impact of [18F]FDG PET/CT on clinical management, as well as its association with clinical, epidemiologic, and biochemical parameters were analyzed. Results: The final diagnoses included infectious diseases in 332 patients (36%), noninfectious inflammatory diseases in 281 (30%), and malignancies in 103 (11%). The cause of FUO remained undiagnosed in 213 patients (23%). [18F]FDG PET/CT scans had positive results for 549 (59%) patients and negative for the remaining 380 patients. The overall [18F]FDG PET/CT sensitivity was 72% (95% CI, 69%-75%), specificity was 85% (95% CI, 79%-89%), positive predictive value was 94% (95% CI, 92%-96%), negative predictive value was 47% (95% CI, 44%-51%), and accuracy was 75% (95% CI, 72%-78%). Predictive markers for a positive PET/CT scan were high C-reactive protein, high erythrocyte sedimentation rate, high neutrophil-to-lymphocyte ratio, the presence of fever at the time of PET, and short duration of prior antibiotic therapy. Moreover, [18F]FDG PET/CT findings directly influenced the clinical management of approximately 75% of patients. Conclusion: [18F]FDG PET/CT is a high-yield diagnostic tool that directly influenced clinical management of approximately 75% of patients with FUO, with optimal performance in patients with elevated inflammatory markers, fever at the time of imaging, and limited prior antibiotic use.
{"title":"Diagnostic Yield of [18F]FDG PET/CT in FUO: An Italian Multicenter Study of 929 Patients.","authors":"Domenico Albano,Francesco Lanfranchi,Matteo Bauckneht,Michela Massollo,Arnoldo Piccardo,Michele Balma,Simona Peano,Virginia Liberini,Alessandro Coccarelli,Silvia Morbelli,Riccardo Laudicella,Giulia Giacoppo,Selene Capitanio,Annalisa Franchini,Alfredo Muni,Alberto Miceli,Roberta Piva,Elisabetta Abenavoli,Flavia Linguanti,Angelina Filice,Rexhep Durmo,Cristina Ferrari,Claudia Battisti,Giuseppe Rubini,Giulia Santo,Elena Busnardo,Arturo Chiti,Desiree Deandreis,Francesco Bertagna","doi":"10.2967/jnumed.125.271525","DOIUrl":"https://doi.org/10.2967/jnumed.125.271525","url":null,"abstract":"Fever of unknown origin (FUO) presents a significant diagnostic challenge because of its wide range of potential causes. The role of [18F]FDG PET/CT in this complex clinical scenario is not yet fully understood. This multicenter retrospective observational study aimed to investigate the diagnostic value and clinical impact of [18F]FDG PET/CT in patients with FUO and to identify specific factors linked to a positive [18F]FDG PET/CT scan. Methods: We retrospectively included 929 patients from 12 centers who underwent [18F]FDG PET/CT for FUO. The final diagnosis for each patient was established on the basis of laboratory, imaging, histopathologic or pathologic examinations, and at least 6 mo of clinical follow-up data. Final diagnoses were classified into 4 categories: infectious diseases, noninfectious inflammatory diseases, malignancies, and unknown causes (no diagnosis). Moreover, the impact of [18F]FDG PET/CT on clinical management, as well as its association with clinical, epidemiologic, and biochemical parameters were analyzed. Results: The final diagnoses included infectious diseases in 332 patients (36%), noninfectious inflammatory diseases in 281 (30%), and malignancies in 103 (11%). The cause of FUO remained undiagnosed in 213 patients (23%). [18F]FDG PET/CT scans had positive results for 549 (59%) patients and negative for the remaining 380 patients. The overall [18F]FDG PET/CT sensitivity was 72% (95% CI, 69%-75%), specificity was 85% (95% CI, 79%-89%), positive predictive value was 94% (95% CI, 92%-96%), negative predictive value was 47% (95% CI, 44%-51%), and accuracy was 75% (95% CI, 72%-78%). Predictive markers for a positive PET/CT scan were high C-reactive protein, high erythrocyte sedimentation rate, high neutrophil-to-lymphocyte ratio, the presence of fever at the time of PET, and short duration of prior antibiotic therapy. Moreover, [18F]FDG PET/CT findings directly influenced the clinical management of approximately 75% of patients. Conclusion: [18F]FDG PET/CT is a high-yield diagnostic tool that directly influenced clinical management of approximately 75% of patients with FUO, with optimal performance in patients with elevated inflammatory markers, fever at the time of imaging, and limited prior antibiotic use.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.2967/jnumed.125.271031
Lisa Glantschnig,Johanna S Enke,Bradley W Schuller,Eric J Fenn,Alexander Dierks,Marianne Patt,Andreas Rinscheid,Robert Seifert,Lena M Unterrainer,Lars H Lindner,Dorit Di Gioia,John W Babich,Alejandro Amor Coarasa,Matthias Friebe,Jacob Y Hesterman,Ralph A Bundschuh,Constantin Lapa
This series of case studies provides the first clinical experience with the fibroblast activation protein-α (FAP)-targeting radiopharmaceutical [177Lu]Lu-RTX-2358 in patients with advanced solid tumors. Methods: Six patients with advanced FAP-expressing solid tumor malignancies and no standard treatment options remaining, underwent radiopharmaceutical therapy (RPT) with [177Lu]Lu-RTX-2358. Biodistribution was monitored using whole-body planar and SPECT/CT imaging, and dosimetric parameters were calculated for critical organs, red marrow, and tumors. Adverse events were graded according to the Common Terminology Criteria for Adverse Events version 5.0. Preliminary antitumor effects were evaluated after 2 RPT cycles. Results: RPT with [177Lu]Lu-RTX-2358 was tolerable with no dose-limiting toxicity. The mean red marrow absorbed dose was 0.131 ± 0.044 Gy/GBq (range, 0.057-0.227 Gy/GBq). The mean kidney absorbed dose was 0.509 ± 0.169 Gy/GBq (range, 0.272-0.893 Gy/GBq). The mean tumor absorbed dose varied across patients, ranging from 0.346 to 2.70 Gy/GBq. Tumor effective half-times ranged from 95.9 to 159.5 h. Disease stabilization was achieved in 4 patients; progressive disease occurred in 2 patients. Conclusion: [177Lu]Lu-RTX-2358 demonstrated a manageable safety profile in a series of patients who were heavily pretreated for their disease. Given a promising therapeutic index as a result of prolonged retention in tumors and clearance from normal organs, further clinical evaluation is warranted.
{"title":"Initial Clinical Experience with [177Lu]Lu-RTX-2358 Radiopharmaceutical Therapy Targeting Fibroblast Activation Protein: Biodistribution, Pharmacokinetics, and Dosimetry.","authors":"Lisa Glantschnig,Johanna S Enke,Bradley W Schuller,Eric J Fenn,Alexander Dierks,Marianne Patt,Andreas Rinscheid,Robert Seifert,Lena M Unterrainer,Lars H Lindner,Dorit Di Gioia,John W Babich,Alejandro Amor Coarasa,Matthias Friebe,Jacob Y Hesterman,Ralph A Bundschuh,Constantin Lapa","doi":"10.2967/jnumed.125.271031","DOIUrl":"https://doi.org/10.2967/jnumed.125.271031","url":null,"abstract":"This series of case studies provides the first clinical experience with the fibroblast activation protein-α (FAP)-targeting radiopharmaceutical [177Lu]Lu-RTX-2358 in patients with advanced solid tumors. Methods: Six patients with advanced FAP-expressing solid tumor malignancies and no standard treatment options remaining, underwent radiopharmaceutical therapy (RPT) with [177Lu]Lu-RTX-2358. Biodistribution was monitored using whole-body planar and SPECT/CT imaging, and dosimetric parameters were calculated for critical organs, red marrow, and tumors. Adverse events were graded according to the Common Terminology Criteria for Adverse Events version 5.0. Preliminary antitumor effects were evaluated after 2 RPT cycles. Results: RPT with [177Lu]Lu-RTX-2358 was tolerable with no dose-limiting toxicity. The mean red marrow absorbed dose was 0.131 ± 0.044 Gy/GBq (range, 0.057-0.227 Gy/GBq). The mean kidney absorbed dose was 0.509 ± 0.169 Gy/GBq (range, 0.272-0.893 Gy/GBq). The mean tumor absorbed dose varied across patients, ranging from 0.346 to 2.70 Gy/GBq. Tumor effective half-times ranged from 95.9 to 159.5 h. Disease stabilization was achieved in 4 patients; progressive disease occurred in 2 patients. Conclusion: [177Lu]Lu-RTX-2358 demonstrated a manageable safety profile in a series of patients who were heavily pretreated for their disease. Given a promising therapeutic index as a result of prolonged retention in tumors and clearance from normal organs, further clinical evaluation is warranted.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.2967/jnumed.125.271296
Moein Moradpour,Abuzar Moradi Tuchayi,Surekha Yadav,Fei Jiang,Irene A Burger,Sabin George Pop,Devaki Shilpa Surasi,Akram Hussein,Ishan Arora,Ana Aparicio,Ivan de Kouchkovsky,Robert R Flavell,Thomas A Hope
Aggressive-variant prostate cancer (AVPC) is characterized by several high-risk features and is typically treated with chemotherapy. In this study, we evaluated the outcomes of patients with AVPC who received prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Methods: This retrospective study included patients with AVPC with metastatic castration-resistant prostate cancer who received PSMA RLT at 3 academic centers. Patients with AVPC were further stratified into 2 subcategories: AVPC-C (clinicopathologic), referring to patients who met AVPC on the basis of clinical or pathologic features, and AVPC-MS (molecular signature), referring to patients who met AVPC criteria on the basis of genomic alterations. Prostate-specific antigen (PSA) response was calculated in the overall cohort, and PSA progression-free survival and overall survival (OS) were calculated in the paired cohort. In the segmentation cohort, SUVmean and total tumor volume were quantified using MIM software. Results: In total, 82 patients were classified as having AVPC, of whom 47 (57%) had AVPC-C and 35 (43%) had AVPC-MS. In the overall cohort, the percentage of patients who had a reduction in PSA of at least 50% or more from baseline was similar between the AVPC and non-AVPC groups (62.1% vs. 60.7%, respectively). In the paired cohort, the median PSA progression-free survival in the AVPC group was 3.2 mo (95% CI, 2.5-5.7 mo), compared with 4.2 mo (95% CI, 3.5-5.1 mo) in the non-AVPC group (P = 0.10). The median OS was shorter in the AVPC group (11.8 mo; 95% CI, 9.7-14.9 mo) compared with the non-AVPC group (13.3 mo; 95% CI, 12.1-15.0 mo; P = 0.04). There was no difference in median OS between AVPC-MS and AVPC-C subgroups (11.9 mo vs. 10.9 mo, respectively; P = 0.8). In the segmentation cohort, there was a trend toward lower SUVmean in patients with AVPC (5.9 vs. 6.6 in patients without AVPC, P = 0.07); however, there was no difference in median total tumor volume between the groups (253.4 mL vs. 298.6 mL, respectively; P = 0.6). Conclusion: Although patients with AVPC exhibited significantly worse OS after PSMA RLT, the percentage of patients treated with PSMA RLT who had a reduction in PSA of at least 50% or more from baseline was similar between the AVPC and non-AVPC groups. These findings support the consideration of PSMA RLT as a treatment option in patients with AVPC who have adequate PSMA expression.
{"title":"Prostate-Specific Membrane Antigen Radioligand Therapy in Patients with Aggressive-Variant Prostate Cancer.","authors":"Moein Moradpour,Abuzar Moradi Tuchayi,Surekha Yadav,Fei Jiang,Irene A Burger,Sabin George Pop,Devaki Shilpa Surasi,Akram Hussein,Ishan Arora,Ana Aparicio,Ivan de Kouchkovsky,Robert R Flavell,Thomas A Hope","doi":"10.2967/jnumed.125.271296","DOIUrl":"https://doi.org/10.2967/jnumed.125.271296","url":null,"abstract":"Aggressive-variant prostate cancer (AVPC) is characterized by several high-risk features and is typically treated with chemotherapy. In this study, we evaluated the outcomes of patients with AVPC who received prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Methods: This retrospective study included patients with AVPC with metastatic castration-resistant prostate cancer who received PSMA RLT at 3 academic centers. Patients with AVPC were further stratified into 2 subcategories: AVPC-C (clinicopathologic), referring to patients who met AVPC on the basis of clinical or pathologic features, and AVPC-MS (molecular signature), referring to patients who met AVPC criteria on the basis of genomic alterations. Prostate-specific antigen (PSA) response was calculated in the overall cohort, and PSA progression-free survival and overall survival (OS) were calculated in the paired cohort. In the segmentation cohort, SUVmean and total tumor volume were quantified using MIM software. Results: In total, 82 patients were classified as having AVPC, of whom 47 (57%) had AVPC-C and 35 (43%) had AVPC-MS. In the overall cohort, the percentage of patients who had a reduction in PSA of at least 50% or more from baseline was similar between the AVPC and non-AVPC groups (62.1% vs. 60.7%, respectively). In the paired cohort, the median PSA progression-free survival in the AVPC group was 3.2 mo (95% CI, 2.5-5.7 mo), compared with 4.2 mo (95% CI, 3.5-5.1 mo) in the non-AVPC group (P = 0.10). The median OS was shorter in the AVPC group (11.8 mo; 95% CI, 9.7-14.9 mo) compared with the non-AVPC group (13.3 mo; 95% CI, 12.1-15.0 mo; P = 0.04). There was no difference in median OS between AVPC-MS and AVPC-C subgroups (11.9 mo vs. 10.9 mo, respectively; P = 0.8). In the segmentation cohort, there was a trend toward lower SUVmean in patients with AVPC (5.9 vs. 6.6 in patients without AVPC, P = 0.07); however, there was no difference in median total tumor volume between the groups (253.4 mL vs. 298.6 mL, respectively; P = 0.6). Conclusion: Although patients with AVPC exhibited significantly worse OS after PSMA RLT, the percentage of patients treated with PSMA RLT who had a reduction in PSA of at least 50% or more from baseline was similar between the AVPC and non-AVPC groups. These findings support the consideration of PSMA RLT as a treatment option in patients with AVPC who have adequate PSMA expression.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-26DOI: 10.2967/jnumed.123.266357
Guillaume Chaussé, Xinchi Hou, Carlos Uribe, Sara Harsini, Jinhe Pan, Heather Saprunoff, Hayley Allan, Hsiou-Ting Kuo, Kuo-Shyan Lin, Don Wilson, François Bénard
Prostate-specific membrane antigen (PSMA) is a validated target for prostate cancer imaging and therapy. [68Ga]Ga-HTK03149 is a PSMA inhibitor designed to improve biodistribution by incorporating a 2-aminoadipic acid moiety as an alternative PSMA binding group. We report the first-in-human safety, biodistribution, and dosimetry evaluation of [68Ga]Ga-HTK03149 and explore organ uptake relevant to future theranostic use. Methods: Men with biochemical recurrence of prostate cancer (prostate-specific antigen, >0.4 ng/mL) after definitive local therapy were enrolled. Each participant underwent a 60-min dynamic PET/CT scan (heart-focused for the first 6 min and then serial whole-body passes), followed by static whole-body acquisitions at 1 and 2 h after injection. In 5 participants, intravenous furosemide (40 mg) was given after the 1-h scan. Volumes of interest were drawn manually, and organ absorbed doses were calculated using OLINDA/EXM version 2.2. Results: Ten men (median age, 68 y; range, 61–74 y; median prostate-specific antigen, 3.3 ng/mL; range, 0.42–9.6 ng/mL) completed imaging without adverse events. Vital signs and laboratory parameters showed no clinically relevant changes. [68Ga]Ga-HTK03149 cleared rapidly from blood and soft tissue, with prominent uptake in the lacrimal and salivary glands, liver, spleen, kidneys, and small intestine, as well as urinary excretion. The kidneys received the highest absorbed dose (0.107 ± 0.020 mGy/MBq), followed by the salivary glands (0.067 ± 0.019 mGy/MBq) and lacrimal glands (0.063 ± 0.026 mGy/MBq). The mean effective dose was 0.012 ± 0.005 mSv/MBq. Forced diuresis significantly reduced the urinary bladder wall dose (0.029 ± 0.0097 vs. 0.056 ± 0.0268 mGy/MBq, P = 0.04) but did not affect the kidney dose (P = 0.99). Lesions (n = 16 in 9/10 patients) showed high uptake and improved contrast at 2 h, with an SUVmax of 7.13 (range, 5.44–10.99) at 1 h versus 9.52 (range, 7.07–13.67) at 2 h (P < 0.001) and a tumor-to-background ratio of 15.74 (range, 10.85–21.09) at 1 h versus 20.42 (range, 12.50–27.51) at 2 h (P < 0.001). Conclusion: [68Ga]Ga-HTK03149 is a safe PSMA-targeted PET radiopharmaceutical with biodistribution and radiation dosimetry comparable to those of existing tracers. Its high tumor uptake and improved delayed lesion contrast support further clinical evaluation for prostate cancer imaging and theranostic applications.
{"title":"First-in-Human Evaluation of [68Ga]Ga-HTK03149, a PSMA-Targeted Tracer for PET Imaging in Prostate Cancer","authors":"Guillaume Chaussé, Xinchi Hou, Carlos Uribe, Sara Harsini, Jinhe Pan, Heather Saprunoff, Hayley Allan, Hsiou-Ting Kuo, Kuo-Shyan Lin, Don Wilson, François Bénard","doi":"10.2967/jnumed.123.266357","DOIUrl":"https://doi.org/10.2967/jnumed.123.266357","url":null,"abstract":"<p>Prostate-specific membrane antigen (PSMA) is a validated target for prostate cancer imaging and therapy. [<sup>68</sup>Ga]Ga-HTK03149 is a PSMA inhibitor designed to improve biodistribution by incorporating a 2-aminoadipic acid moiety as an alternative PSMA binding group. We report the first-in-human safety, biodistribution, and dosimetry evaluation of [<sup>68</sup>Ga]Ga-HTK03149 and explore organ uptake relevant to future theranostic use. <strong>Methods:</strong> Men with biochemical recurrence of prostate cancer (prostate-specific antigen, >0.4 ng/mL) after definitive local therapy were enrolled. Each participant underwent a 60-min dynamic PET/CT scan (heart-focused for the first 6 min and then serial whole-body passes), followed by static whole-body acquisitions at 1 and 2 h after injection. In 5 participants, intravenous furosemide (40 mg) was given after the 1-h scan. Volumes of interest were drawn manually, and organ absorbed doses were calculated using OLINDA/EXM version 2.2. <strong>Results:</strong> Ten men (median age, 68 y; range, 61–74 y; median prostate-specific antigen, 3.3 ng/mL; range, 0.42–9.6 ng/mL) completed imaging without adverse events. Vital signs and laboratory parameters showed no clinically relevant changes. [<sup>68</sup>Ga]Ga-HTK03149 cleared rapidly from blood and soft tissue, with prominent uptake in the lacrimal and salivary glands, liver, spleen, kidneys, and small intestine, as well as urinary excretion. The kidneys received the highest absorbed dose (0.107 ± 0.020 mGy/MBq), followed by the salivary glands (0.067 ± 0.019 mGy/MBq) and lacrimal glands (0.063 ± 0.026 mGy/MBq). The mean effective dose was 0.012 ± 0.005 mSv/MBq. Forced diuresis significantly reduced the urinary bladder wall dose (0.029 ± 0.0097 vs. 0.056 ± 0.0268 mGy/MBq, <em>P</em> = 0.04) but did not affect the kidney dose (<em>P</em> = 0.99). Lesions (<em>n</em> = 16 in 9/10 patients) showed high uptake and improved contrast at 2 h, with an SUV<sub>max</sub> of 7.13 (range, 5.44–10.99) at 1 h versus 9.52 (range, 7.07–13.67) at 2 h (<em>P</em> < 0.001) and a tumor-to-background ratio of 15.74 (range, 10.85–21.09) at 1 h versus 20.42 (range, 12.50–27.51) at 2 h (<em>P</em> < 0.001). <strong>Conclusion:</strong> [<sup>68</sup>Ga]Ga-HTK03149 is a safe PSMA-targeted PET radiopharmaceutical with biodistribution and radiation dosimetry comparable to those of existing tracers. Its high tumor uptake and improved delayed lesion contrast support further clinical evaluation for prostate cancer imaging and theranostic applications.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147292169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-26DOI: 10.2967/jnumed.125.270872
Iman Kiani, Mohammad Amin Siri, Mahan Babaei, Mohammad Mahdi Aliasghari, Saeed Mohammadzadeh, Sara Mohammadi, Ali Salavati
Visual Abstract
视觉文摘
{"title":"Quantitative PSMA PET Biomarkers for Predicting Response to 177Lu-PSMA Therapy in Prostate Cancer: A Systematic Review and Meta-analysis","authors":"Iman Kiani, Mohammad Amin Siri, Mahan Babaei, Mohammad Mahdi Aliasghari, Saeed Mohammadzadeh, Sara Mohammadi, Ali Salavati","doi":"10.2967/jnumed.125.270872","DOIUrl":"https://doi.org/10.2967/jnumed.125.270872","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.125.270872absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147292170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：