The Journal of Nuclear Medicine最新文献

{"title":"Current Developments in Combining External-Beam Radiotherapy and 177Lu-Labeled PSMA Ligands for Prostate Cancer Treatment","authors":"Frederik R. Teunissen, Daniela E. Oprea-Lager, Steffie M.B. Peters, Robert Jan Smeenk, Sandra Heskamp, Johan Bussink","doi":"10.2967/jnumed.125.270465","DOIUrl":"https://doi.org/10.2967/jnumed.125.270465","url":null,"abstract":"<p>The combination of external-beam radiotherapy (EBRT) and ¹⁷⁷Lu-labeled prostate-specific membrane antigen (PSMA) ligands may improve the outcome for specific prostate cancer indications. This review aims to introduce the concept of this combined treatment, provide an overview of preclinical and clinical studies (as well as ongoing trials), and address current challenges and future directions to investigate this emerging therapeutic approach. <strong>Methods:</strong> A comprehensive search was conducted in online research databases (including PubMed) and trial databases (including ClinicalTrials.gov) to gather all relevant preclinical and clinical studies and ongoing trials on the combination of EBRT and ¹⁷⁷Lu-labeled PSMA ligands. <strong>Results:</strong> One completed preclinical study demonstrated increased tumor growth delay and survival with combined EBRT and [¹⁷⁷Lu]Lu-PSMA-617, compared with monotherapies, and one an additive effect. Four clinical reports published results on this combination, including series showing tumor regression in metastatic lesions and a pilot study demonstrating an increased biologically effective dose. Ten ongoing prospective clinical trials with varying designs, patient populations (de novo oligometastatic, oligorecurrent, and locally recurrent), treatment schedules ([¹⁷⁷Lu]Lu-PSMA ligands neoadjuvant, adjuvant, concurrent with EBRT), and radiation doses and fractionation schemes were identified. <strong>Conclusion:</strong> The combination of EBRT and [¹⁷⁷Lu]Lu-PSMA ligands holds promise to improve tumor control without increasing toxicity across various stages of prostate cancer. However, optimal treatment scheduling, dosing regimens, the role of dosimetry, and specific clinical indications require further investigation through robust preclinical and clinical research to guide future clinical trials.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216140","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":"Multicentric Matched-Pair Analysis of Long-Term Hematotoxicity of Peptide Receptor Radionuclide Therapy in Patients Postsplenectomy","authors":"Lisa Steinhelfer, Friederike Jungmann, Lukas Endroes, Helena Lanzafame, Ken Hermann, Christian H. Pfob, Constantin Lapa, Philipp E. Hartrampf, Anna-Lena Dörrler, Andreas K. Buck, Katharina Götze, Patrick Wenzel, Fabian Geisler, Robert Walter, Eva Haneder, Fabian Lohöfer, Bernhard Haller, Rickmer Braren, Matthias Eiber","doi":"10.2967/jnumed.125.270190","DOIUrl":"https://doi.org/10.2967/jnumed.125.270190","url":null,"abstract":"<p>Peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE is an approved treatment for metastatic neuroendocrine tumors (NETs). Although the therapy is effective, hematologic toxicity, particularly leukopenia, remains a significant concern. The spleen, which accumulates radiolabeled somatostatin analogs, may play a critical role in modulating this toxicity. This study investigates whether patients undergoing PRRT after splenectomy exhibit lower hematologic toxicity. <strong>Methods:</strong> This multicenter retrospective study included 68 patients with metastatic NETs treated with PRRT between 2009 and 2022. Splenectomized patients (<em>n</em> = 34) were matched to nonsplenectomized patients on the basis of age, sex, tumor location, grading, metastatic pattern, and treatment cycles. Hematologic parameters (leukocytes, lymphocytes, neutrophils, hemoglobin, and platelets) were assessed at baseline and 12 and 24 mo after PRRT. Hematotoxicity was graded using Common Terminology Criteria for Adverse Events. Statistical analyses included <em>t</em> test, Mann–Whitney <em>U</em> test, and Fisher exact test, with an α of 0.05 and Bonferroni adjustment applied. <strong>Results:</strong> Splenectomized patients had significantly lower rates of leukopenia, with a mean decline of 12.8% in leukocyte count at 24 mo versus 47.2% in nonsplenectomized patients (<em>P</em> &lt; 0.001), and a higher median absolute leukocyte count (7.2 vs. 4.2 × 10³/mm³, <em>P</em> &lt; 0.001). Leukopenia occurred in 2 splenectomized patients compared with 20 in the control group (<em>P</em> &lt; 0.001). Lymphocyte decline was also less pronounced, with higher absolute counts at 24 mo. Platelet counts were consistently higher postsplenectomy, although relative changes over time were not significant. Neutrophil counts and hemoglobin levels remained comparable between groups. <strong>Conclusion:</strong> Splenectomy appears to reduce leukopenia and improve hematologic tolerability in NET patients undergoing PRRT, highlighting the spleen’s role in leukocyte regulation. These patients may better tolerate intensified PRRT regimens, including additional cycles or reinduction, with minimal toxicity. This is particularly relevant for patients with pancreatic NETs, who frequently undergo splenectomy and face a poorer prognosis. Prospective studies are needed to further clarify the spleen’s impact on PRRT-related hematotoxicity and guide treatment optimization.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216092","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":"Multitracer PET to Assess Cardiac Sympathetic Innervation and Vesicular Storage in Lewy Body Diseases","authors":"David S. Goldstein, Courtney Holmes, Yu-Shin Ding","doi":"10.2967/jnumed.125.269840","DOIUrl":"https://doi.org/10.2967/jnumed.125.269840","url":null,"abstract":"<p>Lewy body diseases (LBDs) feature profound myocardial depletion of the sympathetic neurotransmitter norepinephrine. In addition to sympathetic neuronal loss, the norepinephrine deficiency may reflect decreased vesicular sequestration of cytoplasmic catecholamines in dysfunctional but living nerve terminals. To evaluate intraneuronal vesicular storage in patients with LBDs, we retrospectively analyzed multitracer PET data using ¹⁸F-6-fluorodopamine (¹⁸F-DA, a sympathetic neuroimaging agent) and ¹¹C-methylreboxetine (¹¹C-MRB, a ligand for the cell membrane norepinephrine transporter). If there were a vesicular storage defect, then the decrease in ¹⁸F-DA–derived radioactivity would be greater than the decrease in ¹¹C-MRB–derived radioactivity. <strong>Methods:</strong> Twenty-three patients with Parkinson disease or the Lewy body form of pure autonomic failure and 15 controls underwent ¹⁸F-DA dynamic scanning (9 frames; last frame, 10-min duration with midpoint at 25 min) and on a separate day underwent ¹¹C-MRB PET for 45 min (dynamic for 30 min, then a static 15-min frame with midpoint at 38 min). <strong>Results:</strong> All patients in the LBD group had interventricular septal ¹⁸F-DA–derived radioactivity below the range of values in the control group (mean decrease, 75%; <em>P</em> &lt; 0.0001). The LBD group also had a mean decrease of 37% in ¹¹C-MRB–derived radioactivity from the control group in the static frame with midpoint at 38 min (<em>P</em> &lt; 0.0001). At all time points after tracer administration, septal myocardial ¹⁸F-DA/¹¹C-MRB ratios were lower in the LBD group (by 68% at 25 min; <em>P</em> &lt; 0.0001). <strong>Conclusion:</strong> LBDs entail substantially decreased vesicular storage in cardiac sympathetic nerves. This abnormality has direct implications for disease-modifying treatment and prevention strategies, since extant but dysfunctional (“sick-but-not-dead”) neurons may be salvageable.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216139","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":"[225Ac]Ac-PSMA I&T: A Preclinical Investigation on the Fate of Decay Nuclides and Their Influence on Dosimetry of Salivary Glands and Kidneys","authors":"Alexander Wurzer, Baiqing Sun, Samaah Saleh, Julia Brosch-Lenz, Sebastian Fischer, Susanne Kossatz, Kerstin Hürkamp, Wei Bo Li, Matthias Eiber, Alfred Morgenstern, Frank Bruchertseifer, Wolfgang Weber, Calogero D’Alessandria","doi":"10.2967/jnumed.125.269744","DOIUrl":"https://doi.org/10.2967/jnumed.125.269744","url":null,"abstract":"<p>α-therapy with ²²⁵Ac-labeled radioligands targeting prostate-specific membrane antigen (PSMA) has emerged as a promising treatment option for advanced metastatic castration-resistant prostate cancer. Because of α-recoil, the progeny is released from the PSMA-targeted molecule and can undergo redistribution, contributing to off-target toxicity. Here, we report on biodistribution and dosimetry studies of [²²⁵Ac]Ac-PSMA I&amp;T performed in mice to investigate the pharmacokinetics of the radioligand compared with unbound progeny. Moreover, the cellular uptake and externalization kinetics of [²²⁵Ac]Ac-PSMA I&amp;T were compared with those of its ¹⁷⁷Lu-labeled analog. <strong>Methods:</strong> In vitro studies were performed on LNCaP and PC3 PIP cells. Biodistribution studies (performed 10 min to 7 d after injection) were conducted in LNCaP tumor–bearing and healthy mice. Equilibrium uptake was determined 24 h after dissection by quantification of ²²¹Fr (218 keV) and ²¹³Bi (440 keV). Tissues of interest (kidneys, salivary glands, and tumor tissue) were measured immediately after dissection until reaching equilibrium to determine the time-dependent activity distribution of ²²¹Fr and ²¹³Bi. Absorbed doses were calculated using MIRDcalc, assuming decay of the progeny at the site of the first decay versus taking into account redistribution of unbound progeny. <strong>Results:</strong> [²²⁵Ac]Ac-PSMA I&amp;T demonstrated cell-binding characteristics and cellular retention similar to those of [¹⁷⁷Lu]Lu-PSMA I&amp;T. In biodistribution studies, no redistribution of ²²¹Fr and ²¹³Bi was measured from tumor tissue. Higher uptake of ²¹³Bi was found in the kidneys (2-fold higher at 10 min and at 1 h after injection) and salivary glands (1.7-fold and 8.5-fold higher at 10 min and 1 h after injection, respectively) at the time of death compared with equilibrium. This contribution increased the absorbed dose in the kidneys and salivary glands by a factor of 1.3 and 2.5, respectively, assuming uptake of ²²¹Fr and in situ formation of ²¹³Bi. <strong>Conclusion:</strong> The PSMA-targeting characteristics and pharmacokinetics of [²²⁵Ac]Ac-PSMA I&amp;T are similar to those of [¹⁷⁷Lu]Lu-PSMA I&amp;T. The progeny of [²²⁵Ac]Ac-PSMA I&amp;T is trapped in tumor tissue. Uptake of liberated decay products into the salivary glands and kidneys was identified as an additional factor explaining the increased side effects of ²²⁵Ac therapy compared with ¹⁷⁷Lu-based radioligands.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"111 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216137","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":"Optimizing [212Pb]Pb-AB001 Radiopharmaceutical Therapy Schedules in PSMA-Positive Subcutaneous Prostate Cancer Xenografts","authors":"Anna Julie Kjøl Høyvik, Vilde Yuli Stenberg, Rugile Liukaityte, Ada Repetto-Llamazares, Qian Peng, Rina Wangen-Riise, Elisabeth Wiig, Li-Wei Ma, Mona-Elisabeth Revheim, Asta Juzeniene","doi":"10.2967/jnumed.125.270444","DOIUrl":"https://doi.org/10.2967/jnumed.125.270444","url":null,"abstract":"<p>Radiopharmaceutical therapies are typically administered in multiple cycles to improve tolerability, but optimal scheduling remains undefined. Targeted α-therapy with [²¹²Pb]Pb-AB001, a prostate-specific membrane antigen (PSMA)–targeting radioligand, is a promising approach for metastatic prostate cancer. This preclinical study evaluated how treatment schedules and cumulative activities affect therapeutic efficacy and toxicity. <strong>Methods:</strong> Male athymic nude mice bearing subcutaneous PC-3 PIP xenografts received a cumulative activity of 0.8 MBq of [²¹²Pb]Pb-AB001 as a single or as multiple injections at 7-d intervals (Q7d) or 14-d intervals (Q14d). [¹⁸F]PSMA-1007 PET/CT imaging was performed at 1 and 2 wk after treatment. Two additional therapy studies evaluated 0.4 MBq Q7d or every third day (Q3d), with cumulative activities of up to 1.6 MBq. Tumor growth, survival, toxicity, radioligand uptake, and histopathology were evaluated. <strong>Results:</strong> All regimens delayed tumor growth and prolonged survival compared with the controls. Tumor control was improved with the Q7d regimen compared with the Q14d and Q3d regimens. SUV_mean and SUV_max increased significantly 7 d after treatment compared with baseline. Among mice receiving 0.8 MBq cumulatively, the group receiving 4 × 0.2 MBq Q7d showed the best tumor control (median survival, 67 d). Increasing per-cycle activity to 0.4 MBq and extending to 4 cycles Q7d further prolonged median survival to 116 d, with 33% complete responses. Tumor uptake of [²¹²Pb]Pb-AB001 remained consistent across 1–4 injections Q7d. Repeated treatment induced progressive tumor necrosis and edema and reduced PSMA and vascular endothelial growth factor staining. No systemic toxicity was observed at studied activities. <strong>Conclusion:</strong> The efficacy of [²¹²Pb]Pb-AB001 radiopharmaceutical therapy depended on cycle number, interval, and per-cycle activity. Multicycle regimens enhanced tumor control without toxicity, supporting schedule optimization in clinical protocols for [²¹²Pb]Pb-PSMA therapy.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216138","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":"Carotid Artery Image-Derived Blood Time–Activity Curves on the NeuroEXPLORER: Initial Multitracer Validation Against Arterial Sampling","authors":"Tommaso Volpi, Jean-Dominique Gallezot, Shannan Henry, Mark Dias, Nikkita Khattar, Takuya Toyonaga, Kathryn Fontaine, Tim Mulnix, Jiazhen Zhang, Liang Guo, Paul Gravel, Rajiv Radhakrishnan, Ansel T. Hillmer, David Matuskey, Richard E. Carson","doi":"10.2967/jnumed.125.270414","DOIUrl":"https://doi.org/10.2967/jnumed.125.270414","url":null,"abstract":"<p>Image-derived input functions are noninvasive alternatives to arterial blood sampling for PET kinetic modeling, allowing one to measure the whole-blood time–activity curve (BTAC). However, partial-volume effects have limited the use of carotid arteries (CA) to generate image-derived BTACs (ID-BTAC) for brain PET. The NeuroEXPLORER is a next-generation scanner with unprecedented spatial resolution, possibly allowing better CA ID-BTAC extraction. <strong>Methods:</strong> Twelve individuals were scanned on the NeuroEXPLORER with 5 tracers (¹⁸F-FDG, ¹⁸F-SynVesT-1, ¹⁸F-flubatine, ¹¹C-LSN3172176, and ¹¹C-PHNO), and arterial input functions were measured from blood samples. Common carotid (CC) and internal carotid (IC) regions-of-interest (ROIs) were manually segmented on early summed images. ROI diameters were dilated around the CA centerline to evaluate the partial-volume effects. Bias in ID-BTAC area under the curve (AUC) against BTAC was calculated to estimate the ability to recover the gold standard at early (0–10 min) and late times (&gt;10 min). Using ID-BTACs (1-mm ROI diameter), kinetic estimates were generated (<em>K</em>₁<em>, K</em>_i, and <em>V</em>_T), and their bias against arterial input function–based estimates was evaluated. <strong>Results:</strong> For 1–2-mm ROI diameters, early AUC recovery was good (bias: CC, −8% ± 5%; IC, −3 ± 7%). The late AUC was accurately recovered for ¹⁸F-FDG (CC, −9%; IC, −5%), ¹¹C-PHNO (CC, 7%; IC, 4%), and ¹⁸F-SynVesT-1 (CC, −9%; IC, −13%) but not for ¹⁸F-flubatine (CC, 18%; IC, 45%) and ¹¹C-LSN3172176 (CC, 46%; IC, 100%); this poorer agreement corresponded to higher late-time brain-to-blood/face-to-blood activity ratios. The IC outperformed the CC in most cases. ID-BTAC biases translated into small <em>K</em>₁ errors (CC, 5% ± 10%; IC, 3 ± 14%) and larger <em>K</em>_i and <em>V</em>_T errors (CC, −3% ± 20%; IC, −12 ± 25%). <strong>Conclusion:</strong> A simple ID-BTAC extraction approach provided accurate recovery of the early BTAC for all tracers, minimizing spill-out. Late BTAC recovery was more variable, especially with higher background activity. These results highlight how CA ID-BTAC extraction with minimal bias is feasible with ultra-high-resolution brain-dedicated PET scanners.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216141","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":"Influence of Ultra-Low-Dose CT on PET Image Quantification and Visual Assessment","authors":"Samaneh Mostafapour, Joyce van Sluis, Johannes H. van Snick, Walter Noordzij, Gilles N. Stormezand, Marcel J.W. Greuter, Rudi A.J.O. Dierckx, Andor W.J.M. Glaudemans, Riemer H.J.A. Slart, Adriaan A. Lammertsma, Adrienne H. Brouwers, Charalampos Tsoumpas","doi":"10.2967/jnumed.124.269188","DOIUrl":"https://doi.org/10.2967/jnumed.124.269188","url":null,"abstract":"<p>Recent advances in high-sensitivity PET allow for significantly reduced radiation doses, making the CT radiation dose a larger fraction of the total scan dose. This is the first study to the best of our knowledge that evaluates the feasibility and efficacy of an ultra-low-dose CT (ULD-CT) protocol, incorporating a Sn filter, by reducing radiation exposure while maintaining PET image quality and quantitative accuracy in oncology patients. <strong>Methods:</strong> The study involved 29 oncology patients. FDG PET/CT scans were performed using both low-dose CT (LD-CT) and ULD-CT protocols. The ULD-CT protocol used the Sn filter with 100 kVp and 6 mAs, whereas the LD-CT protocol, optimized for PET attenuation correction and anatomic localization, was performed without the Sn filter, using 100–120 kVp and 12–30 mAs. Quantitative and qualitative comparisons of PET images were made, focusing on SUVs, Patlak analysis, and diagnostic quality on different tissues. <strong>Results:</strong> The ULD-CT protocol reduced the CT radiation dose by 97%, from 1.93 ± 0.61 mSv to 0.059 ± 0.026 mSv. SUV comparisons showed relative variations of less than 3%. The net rate of influx values resulting from the Patlak reconstruction showed negligible differences across various tissues between ULD-CT and LD-CT PET reconstructions. Image quality assessments revealed no significant differences between ULD-CT and LD-CT PET reconstructions, with consistently high scores (greater than 4 on a 5-point Likert scale). Lesion detection analysis showed strong intraobserver agreement (intraclass correlation coefficient &gt; 0.85) without significant differences in lesion localization. <strong>Conclusion:</strong> The ULD-CT protocol substantially reduces radiation exposure in PET/CT while maintaining diagnostic quality of PET scans and introducing negligible quantitative effects, thereby paving the way for optimizing CT radiation protocols in PET/CT imaging.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216118","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":"Initial Multicenter Experience with [161Tb]Tb-PSMA in [177Lu]Lu-PSMA–Refractory Metastatic Castration-Resistant Prostate Cancer: Preliminary Results","authors":"Nuriye Ozlem Kucuk, Nazim Coskun, Mine Araz, Nalan Alan Selcuk, Kezban Berberoglu, Elif Cingi Ozdemir, Fikriye Gul Gumuser, Serkan Kuyumcu, Ceren Sezgin, Ozgur Sanli, Yasemin Sanli, Mehmet Ali Nahit Sendur, Yuksel Urun","doi":"10.2967/jnumed.125.270952","DOIUrl":"https://doi.org/10.2967/jnumed.125.270952","url":null,"abstract":"<p>¹⁶¹Tb is a theranostic radionuclide that emits both β⁻ particles and Auger electrons with high linear energy transfer, potentially enhancing cytotoxicity in micrometastatic disease. We report the first multicenter clinical experience of [¹⁶¹Tb]Tb-PSMA in patients with metastatic castration-resistant prostate cancer (mCRPC) refractory to [¹⁷⁷Lu]Lu-PSMA therapy. <strong>Methods:</strong> This prospective, multicenter study included 7 patients with mCRPC who had progressed despite prior androgen receptor pathway inhibitors, taxane-based chemotherapy, and at least 2 cycles of [¹⁷⁷Lu]Lu-PSMA. All patients had PSMA-positive disease without any [¹⁸F]FDG-discordant lesions. Each received 2 cycles of [¹⁶¹Tb]Tb-PSMA (7.4 GBq per cycle, 6-wk interval). Response was assessed with [⁶⁸Ga]Ga-PSMA PET/CT per RECIP 1.0 and prostate-specific antigen kinetics. Posttherapy dosimetry was performed using SPECT/CT imaging at 4 time points. <strong>Results:</strong> Of the 7 patients, 4 (57%) demonstrated objective imaging response and 4 (57%) showed at least a 50% decline in prostate-specific antigen levels. Treatment was well tolerated, with only mild adverse events (grades 1–2) and no toxicity greater than grade 3. Organ dosimetry confirmed favorable absorbed dose distributions. <strong>Conclusion:</strong> [¹⁶¹Tb]Tb-PSMA demonstrated promising molecular and biochemical activity with a favorable safety profile in patients who had progressed after [¹⁷⁷Lu]Lu-PSMA therapy. These preliminary findings support further investigation of ¹⁶¹Tb-based radiopharmaceuticals as next-generation therapeutic options for mCRPC.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"100 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216124","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 Evaluation of [212Pb]Pb-ADVC001: A Prostate-Specific Membrane Antigen–Targeted α-Therapy for Prostate Cancer","authors":"Feifei Liu, Melissa E. Monterosso, Didier Boucher, Stelle Shakti, Kwong Ching Li, Chanwoo Kim, Amber Prior, Abby Sydes, Amelia T. Soderholm, Nicholas Fletcher, Dewan Akhter, Kristofer Thurecht, William Tieu, Kevin Kuan, Aimee Horsfall, Saawan Kumar, Johannes Koehbach, Edward Hammond, Anna Karmann, Stephen Rose, Gary Li, Simon Puttick, Thomas Kryza","doi":"10.2967/jnumed.125.269707","DOIUrl":"https://doi.org/10.2967/jnumed.125.269707","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.125.269707absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141541","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":"First-in-Human Study of [211At]NaAt as Targeted α-Therapy in Patients with Radioiodine-Refractory Thyroid Cancer (Alpha-T1 Trial)","authors":"Tadashi Watabe, Kosuke Mukai, Sadahiro Naka, Hidetaka Sasaki, Takashi Kamiya, Tomoaki Hayakawa, Atsunori Fukuhara, Toru Takano, Yoshifumi Shirakami, Kazuhiro Ooe, Satoshi Shigeno, Satomi Okamura, Kazuho Masumura, Eisuke Hida, Hiromitsu Haba, Atsushi Toyoshima, Kayako Isohashi, Iichiro Shimomura, Noriyuki Tomiyama","doi":"10.2967/jnumed.125.270810","DOIUrl":"https://doi.org/10.2967/jnumed.125.270810","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.125.270810absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141484","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}