The Journal of Nuclear Medicine最新文献

{"title":"Neuroinflammatory PET in Epilepsy: Prospects for Epileptogenic Zone Localization and Presurgical Planning","authors":"Callum Taylor, Bianca Jupp, Lucy Vivash","doi":"10.2967/jnumed.126.272805","DOIUrl":"https://doi.org/10.2967/jnumed.126.272805","url":null,"abstract":"<p>Neuroinflammatory PET offers a direct in vivo means of quantifying neuroinflammatory processes through molecular targets expressed by activated glia, including the 18 kDa translocator protein (TSPO), monoamine oxidase B, and the P2X7 receptor. This review synthesizes current evidence for neuroinflammatory PET in epileptogenic zone (EZ) localization across these and emerging targets. TSPO PET demonstrates ipsilateral uptake in temporal lobe and neocortical epilepsy, detects the EZ in MRI-negative cases, and shows strong concordance with intracranial electroencephalography, with complete resection of TSPO-positive regions associated with seizure-free outcomes. Monoamine oxidase B PET identifies the epileptogenic hippocampus through astrogliosis-specific signaling, whereas P2X7 receptor PET shows promise in preclinical models and ex vivo resected tissue. Emerging targets further expand the repertoire for neuroinflammatory characterization of the EZ. Neuroinflammatory PET has the potential to improve EZ localization, better inform surgical eligibility, and guide resection extent in patients where conventional imaging is insufficient.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148624290","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":"Tumor and Organ Dose Estimates from 177Lu-PSMA-617 Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: Results from the RESIST-PC Phase 2 Trial","authors":"Zachary Ells, Catherine Meyer, Karam Masri, Marc Ryhiner, David Sennung, Koichiro Kimura, David Mirando, Izabela Tworowska, Rouzbeh Esfandiari, Martin S. Allen-Auerbach, Michael Lassmann, Ken Herrmann, Matthias Eiber, Wolfgang P. Fendler, Ebrahim Delpassand, Johannes Czernin, Magnus Dahlbom, Jeremie Calais","doi":"10.2967/jnumed.126.272574","DOIUrl":"https://doi.org/10.2967/jnumed.126.272574","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.126.272574absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148624289","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 Phase 2, Open-Label, Randomized Controlled Trial Evaluating Safety and Efficacy of Dose-Intensified Versus Standard Dosing Regimens of [177Lu]Lu-PSMA-597 in mCRPC (OPTIMAL-PSMA)","authors":"Sobia Khan, Nathan Papa, Takanori Hioki, Megan Crumbaker, Sze-Ting Lee, Andrew Weickhardt, Shikha Sharma, Shraddha Weir, Katharina Luckerath, Edmond Kwan, Louise Emmett","doi":"10.2967/jnumed.126.272714","DOIUrl":"https://doi.org/10.2967/jnumed.126.272714","url":null,"abstract":"<p>OPTIMAL-PSMA aims to determine the safety and efficacy of a dose-intensified (intense induction followed by a maintenance period) regimen of [¹⁷⁷Lu]Lu-PSMA-597 compared with the standard-of-care regimen (every 6 wk for up to 6 doses) in patients with metastatic castration-resistant prostate cancer (mCRPC). <strong>Methods:</strong> OPTIMAL-PSMA is a phase 2, open-label, 2-arm, multicenter, randomized controlled trial of [¹⁷⁷Lu]Lu-PSMA-597, a novel prostate-specific membrane antigen (PSMA) peptide with low nontarget organ dosimetry. A total of 120 patients with mCRPC will be enrolled and randomized 2:1 to receive either a dose-intensified regimen (arm 1) or the standard-of-care regimen (arm 2) of [¹⁷⁷Lu]Lu-PSMA-597. Eligible participants must have mCRPC with disease progression after androgen receptor pathway inhibitor therapy, have received or are not considered medically fit for docetaxel chemotherapy, and demonstrate PSMA-avid disease on PET/CT. Participants assigned to arm 1 will receive early intensified [¹⁷⁷Lu]Lu-PSMA-597 dosing (7.5 or 8.5 GBq on the basis of an interim safety assessment) on days 1, 3, and 15 and during weeks 10, 20, and 30 (6 doses). All participants in arm 2 will receive the standard dose of 7.5 GBq of [¹⁷⁷Lu]Lu-PSMA-597 administered every 6 wk until they are no longer clinically benefiting, for a maximum of 6 doses. Clinical and laboratory safety assessments will be conducted 3 times weekly, with diagnostic CT and bone scans performed at 8 wk and then every 12 wk until radiographic progression. Translational studies incorporate serial multiple-time-point circulating tumor DNA matched with SPECT/CT dosimetry at each time point and PSMA PET at baseline and 8 wk for correlation with clinical outcomes. The primary endpoint is a 90% or greater decline in prostate-specific antigen (PSA) level. Key secondary endpoints include the safety of intensified dosing, a 50% or greater decline in PSA level, radiographic and PSA progression-free survival, and overall survival. Translational endpoints include evaluation of serial circulating tumor DNA, biologic effective dose with intensified versus standard dosing of [¹⁷⁷Lu]Lu-PSMA-597, and evaluation of serial SPECT/CT and PSMA PET/CT for treatment response. <strong>Conclusion:</strong> OPTIMAL-PSMA will determine whether a dose-intensified regimen of [¹⁷⁷Lu]Lu-PSMA-597 is safe and improves depth of response and survival outcomes compared with the standard dosing regimen. The results of this study may redefine the optimal treatment scheduling for PSMA-targeted radiopharmaceutical therapy for patients with mCRPC.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148624291","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":"Evaluating Interim Progression: First Posttherapy 177Lu-PSMA SPECT/CT Relative to Baseline PSMA PET/CT","authors":"Ashwin Singh Parihar, Farrokh Dehdashti, Niharika Pant, Shubha G. Ravindra, Russell Pachynski, Joel Picus, Melissa A. Reimers, Amit Bhatt, Hiram Gay, Wilbur Song, Mark Sundermeyer, Amin H. Jahromi, Christopher A. Swingle, Jeff M. Michalski, Richard L. Wahl, Vikas Prasad","doi":"10.2967/jnumed.126.272545","DOIUrl":"https://doi.org/10.2967/jnumed.126.272545","url":null,"abstract":"<p>Prostate Cancer Working Group 4 recommends using prostate-specific membrane antigen (PSMA) PET for response assessment of patients with androgen pathway receptor modulator–resistant prostate cancer treated with ¹⁷⁷Lu-PSMA-617. For that purpose, the time interval between baseline PSMA PET and initiation of therapy is critical as interim disease progression may influence the performance of PET as a response assessment tool. <strong>Methods:</strong> We visually assessed the frequency of interim disease progression seen on the first posttherapy ¹⁷⁷Lu-PSMA-617 SPECT/CT in 87 patients with androgen pathway receptor modulator–resistant prostate cancer. The time interval between baseline PSMA PET and initiation of therapy, pretherapy prostate-specific antigen (PSA) measures, and treatment outcomes between patients with or without interim progression on SPECT/CT were also compared. <strong>Results:</strong> For the 32 patients (36.8%) with interim progression, the PET to therapy interval (88 d) was significantly greater than those without progression (42 d, <em>P</em> &lt; 0.001) despite adjusting for age, Gleason grade, and PSA doubling time. A time interval between baseline PSMA PET and initiation of therapy exceeding 30 d was seen in approximately 94% of patients with interim progression. PSA response and overall survival were not impacted by interim progression. <strong>Conclusion:</strong> Baseline PSMA PET may not represent the true disease status if the first cycle of ¹⁷⁷Lu-PSMA-617 occurs more than 30 d after baseline PET.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148565044","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":"Outcome Prediction After [177Lu]Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: External Validation of a [68Ga]Ga-PSMA-11 PET–Based Model with [18F]F-Flotufolastat","authors":"Amir Karimzadeh, Cornelia Fütterer, Kimberley Hansen, Ömür Coban, Stefan Hein, Stephan Nekolla, Matthias Heck, Robert Tauber, Bernhard Haller, Andrei Gafita, Wolfgang A. Weber, Matthias Eiber, Isabel Rauscher","doi":"10.2967/jnumed.125.270944","DOIUrl":"https://doi.org/10.2967/jnumed.125.270944","url":null,"abstract":"<p>¹⁷⁷Lu-prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical therapy is an established treatment for metastatic castration-resistant prostate cancer, though responses vary. A prognostic model using [⁶⁸Ga]Ga-PSMA-11 PET–derived parameters was developed to predict therapy outcomes. This retrospective analysis validates the model in an independent cohort imaged with [¹⁸F]F-flotufolastat ([¹⁸F]rhPSMA-7.3 PET) before [¹⁷⁷Lu]Lu-PSMA I&amp;T. <strong>Methods:</strong> In total, 174 consecutive patients treated with [¹⁷⁷Lu]Lu-PSMA I&amp;T at a single center were included in this analysis. The Cox proportional hazards models for overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) and the logistic regression model for PSA response, as proposed in the prognostic model, were applied to our validation data. Model performance was evaluated using the Harrell concordance index (C-index) and calibration plots. OS, PSA-PFS, and PSA response were reported with median values and 95% CI, as well as stratified by published cutoff values into low- and high-risk groups.<strong> Results:</strong> The estimated OS probabilities were 60% (95% CI, 53%–68%) at 12 mo and 40% (95% CI, 33%–49%) at 18 mo. Our validation yielded a C-index of 0.71 (95% CI, 0.67–0.76) for OS prediction compared with a C-index of 0.72 (95% CI, 0.68–0.76) in the validation cohort. For PSA-PFS, the estimated probabilities were 56% (95% CI, 49%–65%) at 3 mo and 34% (95% CI, 27%–42%) at 6 mo, with a C-index of 0.62 (95% CI, 0.57–0.67) compared with a C-index of 0.71 (95% CI, 0.68–0.74) in the validation data. Low-risk patients had significantly longer OS (21.8 vs. 11.6 mo, <em>P</em> &lt; 0.0001) and PSA-PFS (6.9 vs. 2.9 mo, <em>P</em> = 0.003) than did high-risk patients. The prognostic PSA response model showed slightly worse discrimination in our cohort (area under the receiver operating characteristic curve, 0.71; 95% CI, 0.63–0.79) than with the validation data (area under the receiver operating characteristic curve; 95% CI, 0.78, 0.68–0.88). <strong>Conclusion:</strong> Our results indicate accuracy similar to that of the prognostic model for prediction of OS and PSA-PFS and for PSA response in an independent patient population undergoing [¹⁷⁷Lu]Lu-PSMA I&amp;T radiopharmaceutical therapy with [¹⁸F]F-flotufolastat instead of [⁶⁸Ga]Ga-PSMA-11.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"37 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148565042","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":"Clinical Impact and Dynamics of Clonal Hematopoiesis with 177Lu-PSMA-617 Therapy in Advanced Prostate Cancer","authors":"Praful Ravi, Caiwei Zhong, Kimberly J. Perez, Wanling Xie, Virginia Volpe, Gwo-Shu Mary Lee, Jonah Boardman, Emma G. Pittard, Hailey Stoltenberg, Heather Jacene, Lachelle D. Weeks, Adam S. Sperling","doi":"10.2967/jnumed.126.272125","DOIUrl":"https://doi.org/10.2967/jnumed.126.272125","url":null,"abstract":"<p>The prevalence, clinical impact, and clonal dynamics of clonal hematopoiesis (CH) in patients receiving ¹⁷⁷Lu-PSMA-617 (LuPSMA) for metastatic castration-resistant prostate cancer (mCRPC) are unknown. <strong>Methods:</strong> Targeted next-generation sequencing of 21 genes recurrently mutated in CH was performed on DNA extracted from the peripheral blood of patients who received at least 4 cycles of LuPSMA for mCRPC at our institution between 2022 and 2023. Pathogenic somatic mutations with a variant allele fraction of at least 1% were identified using a standardized pipeline. Clinical outcomes pertaining to efficacy (overall survival [OS], measured from date of planned cycle 5) and hematologic toxicity of LuPSMA were collected from the electronic medical record. <strong>Results:</strong> Fifty patients treated with LuPSMA were eligible, with a median follow-up of 23 mo. At least 1 CH variant was detected in 33 patients (66%). The most common mutations were <em>TET2</em> (<em>n</em> = 16), <em>PPM1D</em> (<em>n</em> = 15), and <em>DNMT3A</em> (<em>n</em> = 6). OS was similar in patients with or without CH (12-mo OS, 92% vs. 80%; hazard ratio, 0.89; 95% CI, 0.3–2.68). There was a trend toward greater hematologic toxicity in patients with CH, with a greater need for growth factor support (12% vs. 0%). In patients with serial samples available, the emergence of new clones or expansion of preexisting CH variants was detected in most patients, particularly with <em>PPM1D</em> and <em>TP53</em>-mutant clones. The key limitation was the small sample size and short follow-up. <strong>Conclusion:</strong> CH was highly prevalent and tended to lead to greater hematologic toxicity in patients with mCRPC receiving LuPSMA. Expansion or emergence of DNA damage repair CH clones was very common during and after LuPSMA therapy. Further study of the impact of CH on radiopharmaceutical therapy, particularly when used in earlier prostate cancer disease settings, is warranted.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459795","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":"2025 SNMMI Basic Sciences Summary Session Highlight Lectures: Physics, Instrumentation, and Data Sciences.","authors":"Chi Liu,Ling-Jian Meng,Jinyi Qi,Richard Laforest,Joyita Dutta,R Glenn Wells","doi":"10.2967/jnumed.126.272025","DOIUrl":"https://doi.org/10.2967/jnumed.126.272025","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148462313","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":"Associations of [18F]PI-2620 Binding with Memory and Phosphorylated Tau 217 in Cognitively Unimpaired Older Adults","authors":"Anne Maass, Berta Garcia-Garcia, Niklas Behrenbruch, Beate Schumann-Werner, Eóin N. Molloy, Svenja Schwarck, Michael Rullmann, Anne Hochkeppler, Larissa Fischer, Anna-Therese Büchel, Jose Bernal, Niklas Vockert, Enise I. Incesoy, Wenzel Glanz, Michaela Butryn, Peter Schulze, Kathrin Baldauf, Andrew W. Stephens, Andreas Schildan, Marianne Patt, Gusalija Behnisch, Barbara Morgado, Hermann Esselmann, Constanze I. Seidenbecher, Björn H. Schott, Jens Wiltfang, Henryk Barthel, Osama Sabri, Michael C. Kreissl, Emrah Düzel","doi":"10.2967/jnumed.125.271927","DOIUrl":"https://doi.org/10.2967/jnumed.125.271927","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.125.271927absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459794","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":"Combining an αvβ6-Targeted 177Lu-Based Peptide Receptor Radionuclide Therapy with Olaparib to Boost Therapeutic Efficacy in Pancreatic Cancer","authors":"Tanushree Ganguly, Rebecca E. Harris, Sven H. Hausner, Julie L. Sutcliffe","doi":"10.2967/jnumed.125.271137","DOIUrl":"https://doi.org/10.2967/jnumed.125.271137","url":null,"abstract":"<p>Pancreatic ductal adenocarcinoma is one of the most lethal malignances worldwide, and there remains an urgent need for more effective and less toxic treatment strategies. Integrin α_vβ₆ is a cell-surface receptor that is overexpressed in several malignancies, including pancreatic ductal adenocarcinoma, and plays a key role in invasion and metastasis, making it a promising molecular target for the detection and treatment of many cancers. We investigated a molecularly targeted approach that exploits the overexpression of α_vβ₆ using peptide receptor radionuclide therapy (PRRT) in combination with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. <strong>Methods:</strong> We combined the α_vβ₆-targeted PRRT agent [¹⁷⁷Lu]Lu-DOTA-ABM-5G with olaparib, a PARP inhibitor. The combination therapy was evaluated in vitro in α_vβ₆-positive pancreatic Capan-1 cells by investigating its effect on cell viability, apoptosis induction, cell cycle arrest, and the formation of double-strand breaks. In vivo pharmacokinetic and therapeutic efficacy studies were performed in mice bearing Capan-1 xenograft tumors. <strong>Results:</strong> In vitro, the [¹⁷⁷Lu]Lu-DOTA-ABM-5G was rapidly internalized by α_vβ₆-positive pancreatic Capan-1 cells; in vivo, it was taken up by Capan-1 xenograft tumors in mice. Combination treatment with [¹⁷⁷Lu]Lu-DOTA-ABM-5G and olaparib significantly reduced cell viability (water-soluble tetrazolium salt 1 assay), significantly increased the percentage of cells in the sub-G1 and G2/M phases (cell cycle analysis), and resulted in the greatest number of γ-H2AX foci per cell compared with single-agent treatment. In vivo, the combination treatment delayed tumor growth progression and significantly improved median survival compared with the control and single-agent treatments, with no observed treatment-related adverse events. <strong>Conclusion:</strong> The combination of α_vβ₆-targeted PRRT and PARP inhibition enhanced therapeutic efficacy compared with single-agent treatment. These findings warrant further investigation, particularly given the urgent need for improved treatments for pancreatic cancer.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461837","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 a Composite Score Incorporating Baseline [18F]FDG PET/CT and [68Ga]Ga-PSMA-11 PET/CT When Screening for [177Lu]Lu-PSMA Treatment Eligibility (PROFILE Study)","authors":"Adrien Jougla, Prescillia Nunes, Anne-Laure Giraudet, Anaïs Olivier, Julie Blanc, Alexandre Cochet, Sylvain Ladoire, Jean-Marc Vrigneaud, Lavinia Vija-Racaru, Clément Drouet","doi":"10.2967/jnumed.126.272368","DOIUrl":"https://doi.org/10.2967/jnumed.126.272368","url":null,"abstract":"<p>We investigated the prognostic value of baseline [¹⁸F]FDG and [⁶⁸Ga]Ga-PSMA-11 PET/CT in patients with metastatic castration-resistant prostate cancer treated with [¹⁷⁷Lu]Lu-PSMA-617. <strong>Methods:</strong> In this multicenter retrospective study, the associations between several clinical, biologic, and radiologic parameters and overall survival (OS) were tested in a development cohort using univariable analyses, followed by the construction of a multivariable Cox model. The PROFILE prognostic score was subsequently derived from this model, internally validated, and externally validated in an independent cohort. <strong>Results:</strong> Data from 174 patients from 3 centers were used to construct the multivariable Cox model. Five independent adverse prognostic factors were identified and incorporated into the PROFILE score: an SUV_max exceeding 300% of the PERCIST threshold on [¹⁸F]FDG PET/CT, a “nonhigh” classification on [⁶⁸Ga]Ga-PSMA-11 PET/CT using the visual PSMA tumor–to–salivary gland ratio, a baseline hemoglobin level of 11 g/dL or less, a baseline alkaline phosphatase level of greater than 220 IU/L, and a disease duration not exceeding 100 mo. The PROFILE score stratified patients into 3 risk groups and achieved a Harrell C-index of 0.67 (95% CI, 0.62–0.72). The median OS in the low-, intermediate-, and high-risk groups was 17.2, 13.0, and 8.6 mo, respectively (<em>P</em> &lt; 0.0001). These results were confirmed in 114 patients in an independent, single-center validation cohort, with median OS of 20.4, 14.3, and 8.8 mo (<em>P</em> &lt; 0.0001), respectively, and a C-index of 0.73 (95% CI, 0.68–0.78). <strong>Conclusion:</strong> The PROFILE score offers valuable prognostic information for patients with metastatic castration-resistant prostate cancer when considering the use of [¹⁷⁷Lu]Lu-PSMA-617 therapy.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461834","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}