The Journal of Nuclear Medicine最新文献

{"title":"68Ga-FAPI PET/CT Prevents Futile Surgery and Demonstrates Tumor Biology in Patients with Pancreatic Ductal Adenocarcinoma","authors":"William McGahan, Alexa Chadwick, Karen Lindsay, Brook Gulhane, Melissa J. Latter, Thomas O’Rourke, Paul A. Thomas, David Cavallucci","doi":"10.2967/jnumed.125.270510","DOIUrl":"https://doi.org/10.2967/jnumed.125.270510","url":null,"abstract":"<p>PET/CT using ⁶⁸Ga-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) may detect occult metastases and identify aggressive tumor biology in patients with pancreatic ductal adenocarcinoma (PDAC). We evaluated the impact of ⁶⁸Ga-FAPI PET/CT on surgical treatment in this patient population. <strong>Methods:</strong> Patients with PDAC who were deemed operative candidates after standard CT underwent pretreatment ⁶⁸Ga-FAPI PET/CT and were followed until confirmation of treatment intent. Lymph node ratio in resected tumors was used as a surrogate marker for tumor biology and correlated with the SUV_max of the primary tumor using linear regression. <strong>Results:</strong> Of 16 eligible participants, 5 (31%) had metastases that were not visible on CT scans but were detected with ⁶⁸Ga-FAPI PET/CT, and surgery was prevented. No additional investigations were prompted by ⁶⁸Ga-FAPI PET/CT unless they changed treatment intent. Two participants without metastases on ⁶⁸Ga-FAPI PET/CT did not have surgery because of local progression after neoadjuvant therapy. The SUV_max of the primary tumor at 60 min correlated with the lymph node ratio in resected PDAC (<em>P</em> = 0.04). <strong>Conclusion:</strong> ⁶⁸Ga-FAPI PET/CT may enhance treatment selection in PDAC. Comparative trials are the next step to confirm role in the clinical setting.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255667","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":"SNMMI/EANM/ACNM Procedure Standard/Procedure Guideline on the Use of Molecular Imaging for Renal Mass Characterization","authors":"Steven P. Rowe, Brian M. Shuch, Mark W. Ball, Axel Bex, Mehrbod S. Javadi, Alan Klitzke, Karolien Goffin, Peter Mulders, Neeta Pandit-Taskar, Ashwin Singh Parihar, Benjamin L. Viglianti, Michael A. Gorin, Ken Herrmann","doi":"10.2967/jnumed.125.271332","DOIUrl":"https://doi.org/10.2967/jnumed.125.271332","url":null,"abstract":"<p>Anatomic imaging of renal masses provides limited information on the histology or likely aggressiveness of the tumor, leading to the use of invasive procedures such as renal mass biopsy or empiric partial or radical nephrectomy. Molecular imaging can assist in risk stratification of indeterminate renal masses, potentially contributing to optimal patient decision-making. Two primary approaches have been explored for renal mass molecular imaging. The first is the use of agents that target carbonic anhydrase IX (CAIX), a cell-surface protein that is over-expressed on clear cell renal cell carcinoma (ccRCC) and generally not expressed on other renal tumors. A recent phase III trial (ZIRCON) is widely believed to have laid the groundwork for United States Food and Drug Administration approval of the CAIX monoclonal antibody ⁸⁹Zr-girentuximab. The second approach is the use of mitochondrial imaging agents, most notably ^99mTc-sestamibi, which are lipophilic cations that accumulate in tumors with an abundance of mitochondria with negative charge potential (e.g., oncocytomas and other benign/indolent lesion) and do not accumulate in tumors with multidrug resistance pumps (e.g., ccRCC). The complementary information from ⁸⁹Zr-girentuximab and ^99mTc-sestamibi can provide improved risk stratification. Further, emerging new targeted radiotracers and techniques such as imaging biomarker discovery with artificial intelligence will bolster those concepts. In this manual, we synthesize key data into a recommended approach.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255671","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":"18F-PSMA PET/CT Versus 18F-NaF PET/CT for Staging and Treating Newly Diagnosed High-Risk Prostate Cancer: A Prospective Single-Center Study","authors":"Claus Madsen, Helle D. Zacho, Dan Fuglø, Kayalvily Nielsen, Per Kongsted, Rasmus Bisbjerg, Maria Pedersen, Rikke Broholm, Christian Haarmark, Peter B. Østergren","doi":"10.2967/jnumed.125.270822","DOIUrl":"https://doi.org/10.2967/jnumed.125.270822","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.125.270822absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"110 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255592","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 Initial Imaging and PSA Change with [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A ProsTIC Registry Analysis","authors":"David C. Chen, James P. Buteau, Nathan Papa, Tim Akhurst, Ramin Alipour, Neeraja Bollampally, Anthony Cardin, Michal Eifer, Sebastián Casanueva Eliceiry, Price Jackson, Kerry Jewell, Raghava Kashyap, Grace Kong, Louise Kostos, Aravind Ravi Kumar, Lachlan McIntosh, Elizabeth Medhurst, Javad Saghebi, Shahneen Sandhu, Declan G. Murphy, Ben Tran, Arun A. Azad, Michael S. Hofman","doi":"10.2967/jnumed.125.270804","DOIUrl":"https://doi.org/10.2967/jnumed.125.270804","url":null,"abstract":"<p>[¹⁷⁷Lu]Lu-PSMA-617 radiopharmaceutical therapy improves survival and quality of life in patients with metastatic castration-resistant prostate cancer. We assessed whether patients who did not achieve an early prostate-specific antigen (PSA) decline after the first cycle (C1) benefited from further [¹⁷⁷Lu]Lu-PSMA-617. <strong>Methods:</strong> We analyzed patients with metastatic castration-resistant prostate cancer participating in a registry of [¹⁷⁷Lu]Lu-PSMA-617 (ProsTIC registry, NCT04769817). Patients with a PSA either rising (≥25% increase from baseline) or stable (30% decrease to 25% increase from baseline) within 28 d of starting treatment (C1) and consequently received a second dose (cycle 2) were included. Biochemical response was defined as a PSA decline of more than 50% from baseline (PSA-50) within 20 wk after C1. Quality of life was assessed on 2 validated scales. We evaluated the effect of PSA change and 3 imaging parameters (pretreatment PSMA PET SUV_mean, pretreatment [¹⁸F]FDG PET metabolic tumor volume, and mean total tumor dosimetry on SPECT/CT after C1) with these outcomes and survival time after cycle 2. <strong>Results:</strong> Of 195 patients, 103 met inclusion criteria between January 5, 2021, and March 30, 2023, with an early PSA rise in 31 patients (30%) or stable PSA in 72 patients (70%). Of 103 patients, 45 (44%) achieved PSA-50 by 140 d after C1. Seven of 31 patients (23%) and 38 of 72 patients (53%) with early rising and stable PSA, respectively, had achieved a PSA-50 by 140 d after C1. A PSMA SUV_mean of 10 or more versus an SUV_mean of less than 10 conferred a higher chance of PSA-50 (59% vs. 37%; odds ratio, 2.53; 95% CI, 1.08–5.95). In total, 59 deaths were recorded with a median overall survival of 11.3 mo after cycle 2. [¹⁸F]FDG metabolic tumor volume was the only variable to have a meaningful association with overall survival. Patients with baseline pain scores of 10 or greater according to EORTC QLQ-C30 pain or 2 or greater according to BPI-SF had clinically meaningful reductions in pain in 39 of 55 patients (71%) and 17 of 37 patients (46%), respectively. <strong>Conclusion:</strong> Discontinuing [¹⁷⁷Lu]Lu-PSMA-617 based solely on PSA response after just 1 cycle is not advisable as a substantial number of patients achieve PSA-50 or a reduction in pain. Baseline imaging parameters have prognostic utility and can assist in patient counseling and clinical decision-making.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"122 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145255666","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":"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}