Journal of nuclear medicine : official publication, Society of Nuclear Medicine最新文献

{"title":"Enzyme-Responsive Linkers Enable In Vivo Clearance of Circulating Radioimmunoconjugates.","authors":"Swarbhanu Sarkar, Jonathan M Pham, Andres Fernandez Del Castillo, Lily H Min, Estela Noguera-Ortega, Stephen J Schuster, Mark A Sellmyer","doi":"10.2967/jnumed.126.272755","DOIUrl":"https://doi.org/10.2967/jnumed.126.272755","url":null,"abstract":"<p><p>The application of full-length antibodies as radioimmunoconjugates necessitates a prolonged period between administration and imaging to achieve optimal target visualization. Transcyclooctene-tetrazine chemistry, which enables displacement of radioisotopes from immunoconjugates, can enhance in vivo imaging of target signal relative to background through rapid clearance of circulating, nontargeted radioactivity. An alternative approach, which may accelerate clinical translation, repurposes recombinant enzymes that are approved by the Food and Drug Administration for therapeutic use to trigger cleavage of radioimmunoconjugate linkers. <b>Methods:</b> Radioimmunoconjugate linkers cleavable by β-glucuronidase, carboxypeptidase G2, and tissue plasminogen activator were designed, synthesized, and conjugated to the CD20-targeting antibody rituximab using NOTA or desferrioxamine (DFO) to chelate ⁶⁸Ga or ⁸⁹Zr. CD20-positive Raji cells were incubated with radioimmunoconjugate followed by a cleaving enzyme. Radioimmunoconjugate uptake was measured in CD20-positive Raji cells to confirm immunoreactivity and accumulation in target cells. Biodistribution studies were performed in healthy mice after administration of radioimmunoconjugate and either cognate enzyme or saline to quantify the clearance of radioactivity from the circulation. [⁸⁹Zr]DFO-methotrexate-rituximab was administered to CD1 nude mice carrying subcutaneous Raji xenografts, followed by carboxypeptidase G2 or saline, with subsequent PET imaging and biodistribution studies performed to assess enzyme-mediated changes in imaging contrast. <b>Results:</b> Radioimmunoconjugates were successfully prepared with greater than 95% radiochemical purity. In vitro uptake studies in Raji cells confirmed internalization of radioimmunoconjugates after antigen binding. After internalization, radioimmunoconjugates were no longer susceptible to enzymatic cleavage. Intravenous administration of carboxypeptidase G2 and β-glucuronidase cleared approximately 50% and 70% of injected radioactivity, respectively, from the circulation of non-tumor-bearing mice. In immunocompromised mice bearing subcutaneous Raji xenografts, administration of [⁸⁹Zr]DFO-MTX-rituximab followed by carboxypeptidase G2 enhanced the tumor-to-blood imaging signal by greater than 40% compared with saline-treated controls. <b>Conclusion:</b> The use of Food and Drug Administration-approved enzymes to clear radioactivity from circulating radioimmunoconjugates showed significant efficacy in vivo, providing proof of concept for future clinical applications, particularly in hematologic malignancies.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139834","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":"Patient-Reported Experience and Preferences with Long-Axial-Field-of-View and Total-Body PET/CT: A Prospective, Multicenter Cross-Sectional Survey.","authors":"Ian Alberts, Pavithra Ravi, Sofia Pereira, Marta Assenza, Riccardo Mei, Nadine Colpo, Caroline Williams, Sugama Chicklore, Stefano Fanti, François Bénard, Gary Cook","doi":"10.2967/jnumed.126.272973","DOIUrl":"https://doi.org/10.2967/jnumed.126.272973","url":null,"abstract":"<p><p>Total-body and long-axial-field-of-view PET/CT scanners differ in geometry, scan capability, and access requirements. Understanding patient preferences is essential for protocol design and service planning. <b>Methods:</b> Patients undergoing PET/CT at 3 centers across 3 scanner types completed a structured survey covering scanner perception, physical comfort, claustrophobia, scan duration tolerance, radiation dose and image quality preferences, and travel/access priorities. Group differences were assessed using the Fisher-Freeman-Halton exact test with Cramér φ for effect size. <b>Results:</b> In total, 227 patients completed the survey. Scans were well-tolerated overall, with 96% of respondents reporting no or only minor discomfort. Claustrophobia was uncommon, and neither discomfort (<i>P</i> = 0.07-0.99) nor claustrophobia (<i>P</i> = 0.40-0.75) differed significantly by scanner type or location. When asked how to best tailor protocols, patients strongly prioritized diagnostic image quality; 79% preferred a better-quality scan achieved through longer scan times or a balanced time-dose approach, with only 2% willing to accept lower but acceptable image quality under any circumstance (<i>P</i> < 0.001 by location, φ = 0.29). Most patients (80%) were willing to wait more than 60 min after injection to improve image quality, but this varied significantly by site (<i>P</i> < 0.001, φ = 0.39). Willingness to undergo prolonged dynamic imaging of up to 70 min was expressed by 49% of respondents. Access preferences varied significantly by location (<i>P</i> < 0.001, φ = 0.28), with most patients limiting acceptable travel to 1-3 h and site familiarity being the primary reason for preferring a local center rather than access to higher-quality scanning in a specialized center. <b>Conclusion:</b> PET/CT imaging was well-tolerated across all scanner types. No major discomfort or claustrophobia was encountered with total-body and long-axial-field-of-view PET/CT. Patients valued diagnostic image quality highly and were generally willing to undergo delayed imaging but not scans of longer durations.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139909","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":"Value of Dual-Time-Point [¹⁸F]Fluorocholine PET/CT for Challenging Preoperative Parathyroid Imaging.","authors":"Adrien Latgé, Léonor Chaltiel, Claire Renaud, Laurent Guillon, Solange Grunenwald, Beatrice Herbault Barres, Séverine Brillouet, Mathieu Sinigaglia, Lavinia Vija Racaru","doi":"10.2967/jnumed.126.272492","DOIUrl":"https://doi.org/10.2967/jnumed.126.272492","url":null,"abstract":"<p><p>[¹⁸F]fluorocholine ([¹⁸F]FCH) PET/CT localizes hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism, but the optimal imaging time remains uncertain. We evaluated the added value of a 60-min acquisition after a 10-min acquisition. <b>Methods:</b> Patients with primary hyperparathyroidism who underwent parathyroid surgery after [¹⁸F]FCH PET/CT were included in the study. PET/CT was performed 10 min (early) and 60 min (delayed) after [¹⁸F]FCH injection. Gland location, SUV_max, SUV_peak, and parathyroid-to-thyroid ratio were reported. <b>Results:</b> Among 162 glands surgically removed in 119 patients, the median SUV_max (5.5 vs. 4.9, <i>P</i> < 0.01) and parathyroid-to-thyroid ratio (1.6 vs. 1.4; <i>P</i> < 0.01) were higher at 60 min versus 10 min, whereas the SUV_peak did not significantly differ between acquisition times. Delayed [¹⁸F]FCH PET/CT produced visually superior images for 36 of 113 resected PET-positive glands and changed the clinical interpretation for 23 (19.3%) of 119 cases, revealing an adenoma after a negative early scan in 8 patients. <b>Conclusion:</b> Although early imaging can provide more information, selective delayed imaging offers improved contrast and confidence in negative or equivocal cases.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":""},"PeriodicalIF":9.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140035","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":"Patient Survival and Its Relation to Tumor Absorbed Dose in [¹⁷⁷Lu]Lu-DOTATATE Therapy of Neuroendocrine Tumors.","authors":"Carl Fredrik Warfvinge, Selma Curkic Kapidzic, Johan Gustafsson, Lovisa Jessen, Johanna Svensson, Anna Sundlöv, Katarina Sjögreen Gleisner","doi":"10.2967/jnumed.125.271439","DOIUrl":"10.2967/jnumed.125.271439","url":null,"abstract":"<p><p>[¹⁷⁷Lu]Lu-DOTATATE is an established treatment for metastasized neuroendocrine tumors (NETs). It is postulated that a higher tumor absorbed dose (AD) improves clinical efficacy. The aim of this study was to assess the average AD of the entire tumor burden and analyze its effect on survival outcomes. <b>Methods:</b> This post hoc analysis included 81 patients with metastasized grade 1 and grade 2 NETs treated with [¹⁷⁷Lu]Lu-DOTATATE individualized based on renal dosimetry. Tumor ADs were quantified using quantitative SPECT imaging and mass-weighted averaging across all lesions. Patients were stratified into high- and low-AD groups based on median ADs for cycle 1 and cumulative AD over all cycles. Survival outcomes were assessed using Kaplan-Meier estimates and Cox proportional hazards models. <b>Results:</b> Higher tumor AD was significantly associated with improved progression-free survival and overall survival. In multivariable analysis, patients in the high-AD group had significantly lower hazard ratios (HRs) for progression-free survival (HR, 0.34 for cycle 1; HR, 0.37 for cumulative AD) and overall survival (HR, 0.41 for cycle 1; HR, 0.48 for cumulative AD). Patients with a cumulative AD of 118 Gy or more (top quartile) had significantly improved survival compared with the remaining cohort, without increased toxicity. <b>Conclusion:</b> Mean tumor AD to the entire tumor burden is an independent predictor of survival in patients with grade 1 and grade 2 NETs treated with [¹⁷⁷Lu]Lu-DOTATATE. These findings support the use of tumor dosimetry in treatment planning and suggest that a target AD of around 118 Gy is clinically relevant.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1586-1594"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Nuclear Medicine Through Patient Voices.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":"67 10","pages":"4A"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120914","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":"Imaging xCT with Immuno-PET in Therapy-Resistant Non-Small Cell Lung Cancer.","authors":"Abigail R Barber, Richard S Edwards, Sofia N Dos Santos, Andrea Emanuelli, Will E Tyrrell, Amaia Carrascal-Miniño, Kavitha Sunassee, Israt S Alam, Gary J R Cook, Timothy H Witney","doi":"10.2967/jnumed.126.272920","DOIUrl":"10.2967/jnumed.126.272920","url":null,"abstract":"<p><p>Therapy resistance presents a major clinical challenge in non-small cell lung cancer (NSCLC), contributing to its high mortality rate. Overexpression of the amino acid transporter xCT frequently mediates treatment resistance in NSCLC and can be therapeutically targeted with antibody-drug conjugates. Here, we developed a corresponding immuno-PET radiotracer to noninvasively evaluate xCT expression in NSCLC and visualize the pharmacokinetics of xCT-targeting antibodies. <b>Methods:</b> The specificity of xCT-targeting antibodies, HM30 and HM34, was assessed by Western blot, immunocytochemistry, and internalization studies. Next, these antibodies were conjugated to deferoxamine via their lysine residues and radiolabeled with ⁸⁹Zr. Immunoreactivity was determined by bead- and cell-based binding assays. Preclinical in vivo pharmacokinetics of the ⁸⁹Zr-labeled antibodies were evaluated through longitudinal imaging studies and ex vivo biodistribution using subcutaneous and orthotopic models of NSCLC. <b>Results:</b> Through multiple biochemical methods, we demonstrated excellent target specificity and rapid antibody internalization. Immuno-PET agents [⁸⁹Zr]Zr-DFO-HM30 and [⁸⁹Zr]Zr-DFO-HM34 were produced with good yield and radiochemical purity, with no impact on immunoreactivity. Both agents clearly delineated high xCT-expressing H460 tumors in vivo. Conversely, [⁸⁹Zr]Zr-DFO-HM30 binding was low in low xCT-expressing H1299 tumors. [⁸⁹Zr]Zr-DFO-HM30 imaging and autoradiography of H460 orthotopic lung tumors revealed lesion-specific binding. <b>Conclusion:</b> Our findings provide robust evidence for the use of immuno-PET as a research tool to image elevated xCT expression and visualize tumor penetration of xCT-directed antibodies. This tool can inform the development of enhanced antibody-based therapeutic candidates against treatment-resistant phenotypes to ultimately improve survival outcomes in patients with NSCLC.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1566-1572"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medicine Often Mistakes the Present for the Future.","authors":"Mathias Goyen","doi":"10.2967/jnumed.126.273432","DOIUrl":"10.2967/jnumed.126.273432","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1544-1546"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633357","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":"Radioiodine Spill-Induced Radiation Dermatitis.","authors":"Mahbod Jafarvand, Christiaan Schiepers, Magnus Dalhbom, Angela Castellanos Rieger, Peter George Maliha, Shadfar Bahri","doi":"10.2967/jnumed.125.270585","DOIUrl":"10.2967/jnumed.125.270585","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1683"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889667","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":"Evaluation of 9-Minute Dual-Energy Peak Time-Reduced 360° CZT Total-Body [¹⁷⁷Lu]Lu-PSMA SPECT/CT Imaging with Comparisons to [⁶⁸Ga]Ga-PSMA PET.","authors":"Caroline Boursier, Sébastien Heyer, Abdelaali Zouaoui, Nathaniel Roth, Raphael Blum, Marine Claudin, Pierre Olivier, Pierre-Yves Marie, Antoine Verger, Laetitia Imbert","doi":"10.2967/jnumed.126.272647","DOIUrl":"10.2967/jnumed.126.272647","url":null,"abstract":"<p><p>Eighteen-minute 360° cadmium zinc telluride (CZT) total-body ¹⁷⁷Lu-labeled SPECT acquisitions on the single 113-keV ¹⁷⁷Lu photopeak (SP-18) have been reported to be suitable for monitoring [¹⁷⁷Lu]Lu-PSMA therapy. This study evaluated dual-energy 113- and 208-keV acquisitions with a more than 2-fold increase in acquired counts, allowing acquisition time to be reduced to 9 min (DP-9). <b>Methods:</b> In 20 patients with prostate cancer, 360° CZT total-body ¹⁷⁷Lu-labeled SPECT acquisitions performed after the first [¹⁷⁷Lu]Lu-PSMA therapeutic injection were reconstructed as SP-18, DP-9, and dual-energy 18-min reconstructions (DP-18), all from the same list-mode dataset, and tumor volume and SUV_mean were compared. A standard pretherapy [⁶⁸Ga]Ga-PSMA PET was also used as an external imaging reference. <b>Results:</b> DP-9 yielded tumor volume and SUV_mean that were comparable to those of DP-18. Compared with SP-18, DP-9 produced lower tumor volumes (median percentage difference, -15% [interquartile range, -25% to -12%]) with similar SUV_mean Compared with PET, both SP-18 and DP-9 showed higher SUV_mean (+14% [+7% to + 36%] and +19% [-3% to +38%], respectively), likely reflecting the longer injection-to-imaging delay for SPECT, and higher tumor volumes (+68% [+5% to + 122%] and +47% [-15% to +95%], respectively), consistent with the lower spatial resolution of SPECT. Phantom results were similar for SPECT reconstructions, with PET showing better recovery coefficients for SUV and volume. <b>Conclusion:</b> Dual-energy 360° CZT total-body [¹⁷⁷Lu]Lu-PSMA SPECT/CT enables 9-min acquisitions while providing tumor volume and SUV_mean measurements comparable to those of the previously validated 18-min single-energy protocol. Tumor volumes are lower than those with SP-18 but are closer to PET-derived values. Differences between SPECT and PET mainly reflect the injection-to-imaging time for SUV_mean and the spatial resolution for tumor volume.</p>","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1675-1682"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581774","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":"Update to \"Renal and Multiorgan Safety of ¹⁷⁷Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer in the VISION Dosimetry Substudy\".","authors":"Ken Herrmann, Kambiz Rahbar, Matthias Eiber, Richard Sparks, Nicholas Baca, Bernd J Krause, Michael Lassmann, Walter Jentzen, Jun Tang, Daniela Chicco, Patrick Klein, Lars Blumenstein, Jean-René Basque, Jens Kurth","doi":"10.2967/jnumed.126.265448e","DOIUrl":"10.2967/jnumed.126.265448e","url":null,"abstract":"","PeriodicalId":94099,"journal":{"name":"Journal of nuclear medicine : official publication, Society of Nuclear Medicine","volume":" ","pages":"1689-1691"},"PeriodicalIF":9.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}