The Journal of Nuclear Medicine最新文献

{"title":"Utility of PSMA PET/CT After an Initial Negative Scan: Results from a Prospective Multicenter PSMA PET Registry.","authors":"Ur Metser,Glenn Bauman,Mohammed Rashid,Seyed Ali Mirshahvalad,Andres Kohan,Bo Green,Rosanna Chan,Robert Hamilton","doi":"10.2967/jnumed.126.272204","DOIUrl":"https://doi.org/10.2967/jnumed.126.272204","url":null,"abstract":"There is a paucity of data on the utility of a second prostate-specific membrane antigen (PSMA) PET/CT scan after an initial negative scan in patients with recurrent prostate cancer. The purpose of this study was to assess the utility of a second PSMA PET/CT scan in these patients. Methods: This cohort comprised patients in the PSMA PET Registry for Recurrent Prostate Cancer in Ontario, Canada, who were recruited in 1 of 6 predefined clinical cohorts between October 2018 and September 2022 who had more than 1 PSMA PET/CT scan and whose initial scan was negative. The scan positivity rate, serum prostate-specific antigen (PSA), PSA doubling time, and management change were compared with baseline data. Results: In total, 210 of the 4140 patients in the registry fulfilled the inclusion criteria for the current analysis. The positivity rate of the second PET scan was lower than the baseline PET scan (56.2% [118/210] vs. 68.4% [2832/4140], P = 0.0002). Detection rates were higher in patients with elevated serum PSA (66.9% [107/160] for PSA of 0.5 ng/mL) and a PSA doubling time of less than 12 mo (64.7% [75/116]). Although differences in disease distribution (locoregional vs. distant) were not significant, visceral metastases were more common on the second PET scan (8.5% [10/118] vs. 2.2% [62/2832], P = 0.00002). Management change after a second PET scan was less frequent but remained high (46.4% [83/179]), with more frequent change to salvage therapy for extrapelvic metastases (11% [23/210] vs. 7.3% [302/4140], P = 0.0492). Conclusion: More than half of patients with biochemical failure after primary therapy for prostate cancer who have an initial negative PSMA PET/CT scan may have disease identified on a second PSMA PET/CT scan. The impact of a second PSMA PET/CT scan remains high, with management change necessary for nearly 50% of patients. A second PSMA PET/CT scan after an initially negative scan is more likely to be informative among patients with a PSA greater than 0.5 ng/mL or a PSA doubling time of less than 12 mo.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695069","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}

{"title":"Prognostic Value of PSMA PET-Derived Tumor Burden Stratification in Metastatic Hormone-Sensitive Prostate Cancer.","authors":"Lena M Unterrainer,Honest Ndlovu,Thomas A Hope,Marcus Unterrainer,Johannes Czernin,Mike Sathekge,Jeremie Calais","doi":"10.2967/jnumed.125.271598","DOIUrl":"https://doi.org/10.2967/jnumed.125.271598","url":null,"abstract":"The addition of prostate-specific membrane antigen (PSMA) PET to conventional imaging (CI) leads to both downstaging and upstaging in a substantial proportion of patients with metastatic hormone-sensitive prostate cancer (mHSPC) when applying CHAARTED criteria to both modalities. In this cohort of 42 patients with mHSPC (median follow-up time, 39 mo), PET-derived tumor burden (high-volume, low-volume, and local disease) was more strongly associated with overall survival than was CI-derived tumor burden. Also, the correlation of PET-assessed volumes of disease with progression-free survival exhibited a trend toward improved prognostic performance compared with CI-derived tumor burden (high- and low-volume disease). Stratifying patients by whole-body PSMA PET tumor volume did not yield significant differences. These findings support the implementation of PSMA PET alongside CI into major clinical trials to validate the potential prognostic superiority of PSMA PET-defined tumor burden in patients with mHSPC.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695148","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}

{"title":"Preclinical and First-in-Human Study of Carbonic Anhydrase IX-Targeting Theranostic Pair, [68Ga]Ga/[177Lu]Lu-NYM096, in Clear Cell Renal Cell Carcinoma.","authors":"Jingnan Wang,Xinchun Yan,Meixi Liu,Xueqian Yang,Guoyang Zheng,Xiaoyuan Li,Yuejuan Cheng,Chunmei Bai,Yushi Zhang,Wenjia Zhu,Li Huo","doi":"10.2967/jnumed.125.271604","DOIUrl":"https://doi.org/10.2967/jnumed.125.271604","url":null,"abstract":"Small-molecule PET tracers targeting carbonic anhydrase IX (CAIX) have recently been developed for patients with clear cell renal cell carcinoma (ccRCC). Here, we report the preclinical results and first-in-human study of a CAIX-targeting theranostic pair, [68Ga]Ga/[177Lu]Lu-NYM096, for patients with metastatic ccRCC, aiming to assess its safety, tolerability, dosimetry, and preliminary efficacy. Methods: The in vivo biodistribution of [68Ga]Ga-NYM096 was evaluated in mice bearing OS-RC-2 xenografts. The therapeutic efficacy of [177Lu]Lu-NYM096 was assessed with a dose escalating from 8.1 to 74 MBq. Patients with metastatic ccRCC who had disease progression after standard therapy were prospectively enrolled. Serial whole-body [68Ga]Ga-NYM096 PET/CT scans were performed to evaluate biodistribution and dosimetry. Patients with positive CAIX expression entered the therapeutic phase and received [177Lu]Lu-NYM096 following a standard 3-plus-3 dose escalation design that started from 1.85 GBq. Serial whole-body planar imaging was performed after the first therapy cycle. Safety, dosimetry, and preliminary efficacy were evaluated. Results: High tumor accumulation of [68Ga]Ga/[177Lu]Lu-NYM096 was observed in OS-RC-2 xenograft tumor models. Moreover, [177Lu]Lu-NYM096 was well tolerated and demonstrated a significant dose-dependent tumor suppression effect. In the 2 patients, [68Ga]Ga-NYM096 demonstrated excellent tumor uptake, with an SUVmax of 330.0 at 1 h postinjection. Subsequent [177Lu]Lu-NYM096 treatment demonstrated no evidence of nephrotoxicity, hepatotoxicity, or pancreatic toxicity. Patient 1 experienced grade 1 gastric side effects and anemia, whereas patient 2 developed grade 3 radiation-induced gastritis. Follow-up [68Ga]Ga-NYM096 PET/CT evaluations showed evidence of tumor response to [177Lu]Lu-NYM096 treatment. Conclusion: This is early evidence that the CAIX-targeting theranostic pair [68Ga]Ga/[177Lu]Lu-NYM096 is feasible, offering a strategy for patients with end-stage ccRCC. The gastric toxicity proposes a significant challenge for CAIX-targeting radiopharmaceutical therapy.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695068","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}

{"title":"Dynamic Total-Body PET Imaging Unfolds [11C]Choline Kinetics and Dosimetry in Primary Hyperparathyroidism.","authors":"Irene Brusa,Miriam Santoro,Daniele Dall'Olio,Giuseppe Arturo Fuso,Federico Zagni,Marta Assenza,Emilia Fortunati,Stefano Emiliani,Veronica Serena Cabitza,Elena Tabacchi,Andrea Farolfi,Riccardo Mei,Cristina Nanni,Paolo Castellucci,Letizia Calderoni,Lidia Strigari,Gastone Castellani,Stefano Fanti","doi":"10.2967/jnumed.125.270518","DOIUrl":"https://doi.org/10.2967/jnumed.125.270518","url":null,"abstract":"This study investigated the biodistribution profile, kinetic constants, and dosimetry of [11C]choline in patients with primary hyperparathyroidism (pHPT) using total-body dynamic PET (dPET) imaging, to establish a baseline and standard reference for clinical practice. Methods: A 50-min dPET acquisition followed by a 20-min static acquisition at 100 ± 10 min postinjection was performed on 6 patients with a clinical diagnosis of primary hyperparathyroidism. Whole-body [11C]choline distribution and pharmacokinetics were evaluated by SUV, tissue uptake, organ-absorbed doses, and, finally, multitime graphical analysis and kinetic modeling with compartment models. Results: Rapid whole-body uptake of [11C]choline was observed, with adequate image quality for presurgical localization of parathyroid adenomas seen from 5 min postinjection onward. Average uptake values after 50 min for liver (17.61% ± 2.82%) and bowel (5.77% ± 1.80%), compared with kidneys (2.77% ± 0.24%) and urinary bladder (0.21% ± 0.16%), suggested alternative excretion pathways for [11C]choline other than renal clearance. Gallbladder (0.019 ± 0.004 mGy/MBq), liver (0.037 ± 0.008 mGy/MBq), pancreas (0.022 ± 0.005 mGy/MBq), kidneys (0.016 ± 0.005 mGy/MBq), and spleen (0.023 ± 0.009 mGy/MBq) were the organs with the highest observed effective doses. These organs also showcased extreme values among [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text], which provide them with the most distinctive kinetic patterns. Parathyroid adenomas exhibited significantly higher k 3, Ki , and distribution volume, and lower K 1, than reference thyroid tissue (P < 0.05). Conclusion: The high adenoma-to-background uptake of [11C]choline observed 5 min postinjection onward may facilitate swift imaging protocols. The total-body dynamic approach further highlighted the pivotal role of liver metabolism, minimal renal excretion, and unique kinetic behaviors of parathyroid adenomas. These data advance our understanding of [11C]choline's uptake and may serve as a reference for future dPET studies.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695100","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}

{"title":"Circulating Tumor DNA Genomic Profiling in 223Ra-Treated Metastatic Castration-Resistant Prostate Cancer: The KYUCOG-1901 Study.","authors":"Masaki Shiota,Maki Fujiwara,Takayuki Sumiyoshi,Hideki Enokida,Tomomi Kamba,Tsukasa Igawa,Naoya Masumori,Hirotsugu Uemura,Toshiyuki Kamoto,Katsuyoshi Higashijima,Kensuke Mitsunari,Hiroji Uemura,Takashi Kobayashi,Shusuke Akamatsu,Shoji Tokunaga,Takuro Isoda,Kousei Ishigami,Masatoshi Eto","doi":"10.2967/jnumed.126.272073","DOIUrl":"https://doi.org/10.2967/jnumed.126.272073","url":null,"abstract":"Circulating tumor DNA (ctDNA) testing has emerged as a cancer precision medicine approach. We investigated the genomic landscape and clinical utility of ctDNA in patients receiving 223Ra dichloride for bone metastatic castration-resistant prostate cancer (mCRPC). Methods: This prospective, observational, multicenter study enrolled patients treated with 223Ra for bone mCRPC. Targeted sequencing of cell-free DNA from plasma at baseline and end of treatment (EOT), along with paired leukocyte DNA, was performed using an 88-gene panel. Associations between ctDNA profiles and clinical outcomes, including biomarker response, radiographic progression-free survival (rPFS), and overall survival (OS), were analyzed. Results: Of 93 patients analyzed, ctDNA was successfully profiled in 84 baseline and 74 EOT samples, with matched data available for 68 patients. A ctDNA fraction of at least 5%, as well as TP53 alteration, PTEN alteration, and cell cycle pathway alterations at baseline were significantly associated with shorter rPFS and OS. Dynamic changes in ctDNA fraction and PTEN alteration between baseline and EOT correlated with distinct rPFS and OS. Conclusion: This study suggests the clinical utility of ctDNA profiling as both a prognostic and a monitoring tool in patients with bone mCRPC treated with 223Ra. The findings obtained in this study raise the possibility that ctDNA could contribute to future strategies for risk stratification or treatment monitoring during 223Ra therapy.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695070","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}

{"title":"Patterns of Progression After Peptide Receptor Radiopharmaceutical Therapy.","authors":"Moein Moradpour,Abuzar Moradi Tochayi,Sina Houshmand,Stellamaris Nwihim,Fei Jiang,Surekha Yadav,Sheila Lindsay,Emily K Bergsland,Thomas A Hope","doi":"10.2967/jnumed.125.270483","DOIUrl":"https://doi.org/10.2967/jnumed.125.270483","url":null,"abstract":"[177Lu]Lu-DOTATATE has been approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). It is often thought that NET progression may result in somatostatin receptor (SSTR)-negative disease because of the elimination of SSTR-positive clones. This study aimed to assess the patterns of progression and SSTR uptake in patients with NETs after peptide receptor radionuclide therapy (PRRT). Methods: In this retrospective study, we evaluated patients with NETs who received PRRT between 2016 and 2024. Imaging findings and medical oncology notes were reviewed to identify and characterize disease progression. Using postprogression SSTR PET scans, the SUVmax of the progressed lesion was measured, and qualitative radiotracer uptake was compared with baseline. Results: In total, 195 patients were treated with PRRT, and progression occurred in 107 patients (54.9%). The liver was the dominant site of progression (65 patients, 60.7%), followed by bone (27 patients, 25.3%). The mean ± SD SUVmax of the hottest lesion on SSTR PET was 54.3 ± 41.0 at baseline and 46.0 ± 35.5 after disease progression (P = 0.02). Qualitatively, postprogression SSTR PET showed equal uptake in 59.7% of patients, higher uptake in 18.2%, and reduced uptake in 19.5% compared with baseline. SSTR-negative disease was observed in 4 patients (3.7%). SSTR PET identified progression that was not seen on conventional imaging in 50 patients (46.7%). Conclusion: Most patients who experienced progression after PRRT continued to express SSTR, with a decrease in SUVmax SSTR-negative disease was rare, indicating that the majority remained eligible for retreatment with SSTR-targeted radioligands. SSTR PET identified disease progression in 46.7% of patients, emphasizing its essential role in detecting disease progression, particularly in nonmeasurable disease, such as that in bone.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641490","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}

{"title":"Brain Metabolic Activity Measured by [18F]FDG PET/CT Predicts Survival in Patients with Advanced Non-Small Cell Lung Cancer.","authors":"Julie Auriac,Ghada Lemoudda,Narinée Hovhannisyan-Baghdasarian,Manuel Pires,Lalith Kumar Shiyam Sundar,Paulette Salamoun-Feghali,Romain-David Seban,Nina Jehanno,Christophe Nioche,Marie Luporsi,Thomas Beyer,Alain Livartowski,Nicolas Girard,Irène Buvat,Fanny Orlhac","doi":"10.2967/jnumed.125.271400","DOIUrl":"https://doi.org/10.2967/jnumed.125.271400","url":null,"abstract":"[18F]FDG PET/CT images play a key role in the management of patients with non-small cell lung cancer (NSCLC). In these scans, the focus is on detected tumors and their characteristics, neglecting information from other organs or tissues. We investigated whether the mean brain [18F]FDG uptake (brain SUVmean) is associated with overall survival (OS) in patients with advanced NSCLC. Methods: This retrospective study included patients with advanced NSCLC who underwent pretreatment [18F]FDG PET/CT scans between 2010 and 2023. Clinical and biologic data, tumor radiomic features, and brain SUVmean were collected. The ability of these features to predict OS was evaluated using univariable and multivariable Cox regression models. The correlation between brain SUVmean and clinical, imaging, and blood biomarkers was investigated using Spearman correlation coefficients. Results: Patients were chronologically divided into a discovery set (n = 234; mean age, 64 ± 11 y) and test set (n = 146; mean age, 66 ± 11 y). In the discovery set, univariable analysis showed that high brain SUVmean (greater than or equal to the median) was associated with longer OS (hazard ratio [HR], 0.83; 95% CI, 0.76-0.92; P < 0.001). Brain SUVmean was significantly lower in patients who died within 1 y compared with those who were still alive at the same time point (median brain SUVmean, 4.9 ± 1.4 vs. 5.7 ± 1.5, respectively; P < 0.001). Multivariable analysis revealed that brain SUVmean was an independent prognostic factor for OS (HR, 0.89; 95% CI, 0.80-0.98; P = 0.02), which was confirmed in the test set (P < 0.001). Brain SUVmean was independent of the radiomic features quantifying tumor involvement (r < 0.24, n = 380) and significantly correlated but complementary to several blood biomarkers including C-reactive protein (r = -0.37, n = 110 patients). The prognostic significance of brain SUVmean persisted in patients without brain metastases (P < 0.001). Conclusion: Low brain metabolic activity was associated with increased mortality in patients with advanced NSCLC. Brain SUVmean was an independent prognostic factor that may aid in patient stratification, although its interpretation requires further investigation.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641491","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}

{"title":"A Novel CD147-Targeting Nanobody for Immuno-PET Imaging of Liver Cancer.","authors":"Divya M Nambiar,Thomas J Esparza,Woonghee Lee,Joon-Yong Chung,Colleen P Olkowski,Behnaz Ghaemi,Falguni Basuli,Jianfeng Shi,Kwamena E Baidoo,Julia Sheehan-Klenk,Hima Makala,Hongwei H Zhang,Joshua M Farber,Peter L Choyke,Freddy E Escorcia,Orit Jacobson","doi":"10.2967/jnumed.125.271565","DOIUrl":"https://doi.org/10.2967/jnumed.125.271565","url":null,"abstract":"Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with a 5-y survival rate of approximately 20%. Many patients undergo locoregional therapy, and distinguishing viable tumor from treated necrotic tissue presents a significant clinical challenge with conventional imaging. CD147, a transmembrane glycoprotein overexpressed in approximately 60% of HCC tumors with minimal expression in normal liver, represents a promising target for tumor-selective molecular imaging to address this unmet clinical need. We aimed to develop and characterize a CD147-targeted nanobody-based PET imaging agent compatible with same-day clinical imaging workflows. Methods: We constructed a phage-display library from a llama immunized with recombinant human CD147. CD147-selective nanobodies were isolated through iterative immunopanning and characterized by enzyme-linked immunosorbent assay, biolayer interferometry, and flow cytometry using isogenic CD147-positive and CD147-knockout liver cancer cell lines. The lead candidate, denoted as DMN1, was radiolabeled with 18F via [18F]FPy pyridine-based prosthetic group conjugation. The radiolabeled nanobody was evaluated in cellular assays and further characterized in vivo using PET/CT imaging and biodistribution studies in subcutaneous and orthotopic murine HCC models. Results: DMN1 demonstrated low binding affinity to human CD147 (K D = 0.71 ± 0.1 nM, enzyme-linked immunosorbent assay), with specificity confirmed in CD147-positive versus CD147-negative xenografts. [18F]FPy-DMN1 was synthesized with high radiochemical purity (>98%), a molar activity of 3,700-11,100 GBq/μmol, and good serum stability (87% intact in mouse serum at 3 h). In vivo, [18F]FPy-DMN1 showed robust tumor accumulation in CD147-positive (3.82 ± 0.93 %IA/g) versus CD147-negative tumor xenografts (0.21 ± 0.02 %IA/g), with excellent tumor-to-background ratios at 2 h postinjection (tumor-to-blood ratio, 18.7 ± 3.9; tumor-to-muscle ratio, 52.6 ± 22.1). In orthotopic liver tumors, [18F]FPy-DMN1 enabled clear tumor visualization with striking contrast at 3 h postinjection, whereas the control nanobody showed no tumor localization. Conclusion: [18F]FPy-DMN1 is a novel CD147-specific nanobody-based PET imaging agent that demonstrates high target specificity and favorable pharmacokinetics for same-day imaging. Its rapid blood clearance, high tumor-to-background ratios, and successful visualization of orthotopic liver tumors support further development of this agent for imaging and monitoring treatment response in patients with liver cancer.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"21 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641492","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}

{"title":"Response to the FDA Dosage Optimization Draft Guidance for Radiopharmaceutical Therapies.","authors":"Ana P Kiess,John J Sunderland,Peter J H Scott,Thomas A Hope","doi":"10.2967/jnumed.126.272138","DOIUrl":"https://doi.org/10.2967/jnumed.126.272138","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641493","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}

{"title":"Development of Dar3A Chelator and Construction of FAP-Targeted PET Probe as Proof of Concept and for First-in-Human Evaluation.","authors":"Renda Li,Rui Cao,Guojin Zhang,Longyong Ding,Chaoquan Lai,Entao Liu,Kun Qian,Boyu Tan,Jiamin Zhu,Miaomiao Song,Renli Luo,Jin Du,Quanyong Luo,Chunrong Qu,Lei Jiang,Zhen Cheng","doi":"10.2967/jnumed.125.271421","DOIUrl":"https://doi.org/10.2967/jnumed.125.271421","url":null,"abstract":"Developing novel radiopharmaceuticals for cancer theranostics has recently attracted extensive interest. Bifunctional chelators are key components of many radiometal-based radiopharmaceuticals. For the established 68Ga/177Lu theranostic pair, the commonly used chelator DOTA suffers from some issues, such as the requirement for heating during radiolabeling and slow chelation kinetics. The limitations highlight the need to develop new bifunctional chelators. Methods: The novel macrocyclic chelator 2-[11,27-bis(carboxymethyl)-34,36-dihydroxy-7,23-dimethyl-3,11,19,27,33,35-hexaazapentacyclo[27.3.1.15,9113,17121,25]hexatriaconta-1(33),5(36),6,8,13,15,17(35),21(34),22,24,29,31-dodecaen-3-yl]acetic acid (Dar3A) was synthesized and modified with a pendant arm for bioconjugation. A comprehensive comparison with DOTA was performed, including titration experiments to assess thermodynamic stability and radiolabeling studies to evaluate the efficiency of 68Ga and 177Lu labeling. For a proof of concept, Dar3A was conjugated with a fibroblast activation protein-targeted moiety derived from fibroblast activation protein inhibitor-04 and radiolabeled with 68Ga to prepare [68Ga]Ga-SMIC-3101. The resulting 68Ga-labeled radiotracer was further evaluated in cellular assays, animal models, and human subjects (3 healthy volunteers and 1 patient with esophageal cancer). Results: Dar3A exhibited superior radiolabeling efficiency with 68Ga and 177Lu compared with DOTA, and [68Ga]Ga-SMIC-3101 was obtained with a molar activity of 28.7 MBq/nmol. In U87MG tumor-bearing mice, [68Ga]Ga-SMIC-3101 exhibited enhanced tumor uptake (12.73 ± 1.68 and 10.64 ± 2.88 %ID/g at 2 and 4 h, respectively), significantly exceeding that of DOTA-based [68Ga]Ga-FAPI-04 (0.66 ± 0.22 and 0.51 ± 0.10 %ID/g, respectively). Moreover, the first-in-human study demonstrated that [68Ga]Ga-SMIC-3101 was safe, with physiologic excretion occurring primarily via the hepatobiliary system, and clearly visualized primary and metastatic esophageal cancer lesions. Conclusion: Dar3A is a promising bifunctional chelator for radiolabeling and bioconjugation, supporting theranostic radiopharmaceutical development.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641739","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}