The Journal of Nuclear Medicine最新文献

{"title":"Imaging the Activity of Efflux Transporters at the Blood–Brain Barrier in Neurologic Diseases: Radiotracer Selection Criteria","authors":"Nicolas Tournier, Oliver Langer","doi":"10.2967/jnumed.124.269322","DOIUrl":"https://doi.org/10.2967/jnumed.124.269322","url":null,"abstract":"<p>Efflux transporters of the adenosine triphosphate–binding cassette (ABC) superfamily, such as P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), are highly expressed at the blood–brain barrier (BBB), where they contribute to maintaining brain homeostasis. P-gp may serve as an imaging biomarker to assess the contribution of BBB functionality rather than integrity to the onset or progression of various neurologic diseases. Considerable efforts have been made to develop radiolabeled P-gp substrates to assess cerebral P-gp activity with PET. However, initially developed radiotracers have limited clinical utility as they lack sensitivity to detect moderate, physiologically relevant changes in cerebral P-gp activity. Learning from this molecular imaging area has called for specific criteria, different from those classically used for other central nervous system targets, for developing and selecting suitable PET tracers to study ABC transporter activity at the BBB in different neurologic diseases.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517875","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 FDG PET Metabolic Parameters Before and After 42 Gy of Radiochemotherapy in Patients with Inoperable Stage III Nonsmall Cell Lung Cancer","authors":"Pierre Vera, Philippe Giraud, Sébastien Hapdey, Pierrick Gouel, Orianne Jan, Paul Le Roux, Alexandra Langlais, Emilie Lévêque, Florence Le Tinier, Anaïs Olivier, Etienne Martin, Alina Berriolo-Riedinger, Nicolas Pourel, Jean Marc Broglia, Pierre Boisselier, Sophie Guillemard, Naji Salem, Isabelle Brenot-Rossi, Camilo Garcia, Céline Berthold, Etienne Giroux-Leprieur, Damien Moreau, Sophie Guillerm, Khadija Benali, Laurent Tessonnier, Clarisse Audigier-Valette, Delphine Lerouge, Elske Quak, Carole Massabeau, Frédéric Courbon, Maxime Loo, Anne Larrouy, Nadia Ghazzar, Philippe Chaumet-Riffaud, Elodie Amour, Gérard Zalcman, Romain Modzelewski, Sébastien Thureau","doi":"10.2967/jnumed.124.268499","DOIUrl":"https://doi.org/10.2967/jnumed.124.268499","url":null,"abstract":"<p>The purpose of this study was to assess the prognostic value of ¹⁸F-FDG PET parameter variation between baseline and 42 Gy (PET2) of radiochemotherapy at 6 mo and 1 y of evaluation in patients with stage III inoperable nonsmall cell lung cancer based on RECIST 1.1. <strong>Methods:</strong> In total, 158 patients in a prospective multicenter phase II/III study were analyzed. Patients were randomized into 2 groups: an experimental arm (group A) and a standard arm (group B). Patients from group A with residual metabolism on PET2 (group A+) at 42 Gy received a radiation boost (74 Gy). Patients without residual uptake on ¹⁸F-FDG PET at 42 Gy (group A−) and patients in group B received a standard radiotherapy dose (66 Gy). We compared group A with group B. The ¹⁸F-FDG PET parameters SUV_max, SUV_mean, SUV_peak, peak SUV normalized on lean body mass, mean SUV normalized on lean body mass, total lesion glycolysis, total metabolic tumor volume (MTV) (tumor and nodes), and tumor MTV were measured. All patients were evaluated with RECIST 1.1 using CT at 6 mo and 1 y after radiochemotherapy. Progression-free survival and overall survival were evaluated. <strong>Results:</strong> Except for the radiotherapy dose (<em>P</em> &lt; 0.001), patient demographic characteristics were similar between the 2 groups (A vs. B). All ¹⁸F-FDG PET uptake and volume parameter measurements were correlated. Therefore, only the change in SUV_max (ΔSUV_max) and total MTV were selected for the analysis. There was no significant difference in any variable between the 2 groups. In the multivariate analysis, ΔSUV_max appeared to be the most important prognostic factor for overall survival, and SUV_max of PET2 appeared to be the most important prognostic factor for progression-free survival. <strong>Conclusion:</strong> ¹⁸F-FDG PET at 42 Gy can be used to identify good responders to radiochemotherapy in patients with inoperable stage III nonsmall cell lung cancer. The SUV_max of PET2 and ΔSUV_max are independent prognostic factors.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"9 12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518496","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":"177Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial","authors":"Andreas Hallqvist, Elva Brynjarsdóttir, Tomas Krantz, Marie Sjögren, Johanna Svensson, Peter Bernhardt","doi":"10.2967/jnumed.124.268902","DOIUrl":"https://doi.org/10.2967/jnumed.124.268902","url":null,"abstract":"<p>This phase I trial aimed to assess the feasibility and toxicity of combining the poly(adenosine diphosphate–ribose) polymerase inhibitor olaparib with ¹⁷⁷Lu-DOTATATE in patients with somatostatin receptor–positive tumors, with the goal of enhancing treatment efficacy through the inhibition of tumor cell DNA repair mechanisms. <strong>Methods:</strong> Eighteen patients were enrolled, mostly with pancreatic or small intestinal neuroendocrine tumors or atypical lung carcinoids. Patients received a standard dose of ¹⁷⁷Lu-DOTATATE (7,400 MBq) for up to 4 cycles, combined with escalating doses of olaparib (50–300 mg twice a day [BID]). The primary objective was to evaluate toxicity using National Cancer Institute Common Toxicity Criteria version 5.0. Secondary objectives included time to progression, overall survival, response rate, and dosimetry variables. <strong>Results:</strong> The combination of olaparib and ¹⁷⁷Lu-DOTATATE was generally well tolerated. Five patients did not complete the 4 cycles because of progression, noncompliance, and carcinoid crisis after the first ¹⁷⁷Lu-DOTATATE infusion. Among the remaining patients, thrombocytopenia was the primary dose-limiting toxicity, observed in 3 patients at the 300-mg dose level. Other toxicities were mild, predominantly low-grade bone marrow suppression, nausea, and fatigue. <strong>Conclusion:</strong> This study demonstrates that combining olaparib with ¹⁷⁷Lu-DOTATATE is feasible, with toxicity primarily related to thrombocytopenia. On the basis of the findings, we recommend a starting dose of 200 mg BID for future studies, with the potential to escalate to 300 mg BID depending on patient tolerance. Further investigation in larger, randomized trials is warranted to assess the clinical efficacy of this combination and optimize dosing strategies.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518501","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":"The Role of PSMA PET Parameters as Biomarkers for Response to PSMA-Targeted Radiopharmaceutical Therapy","authors":"Vishnu Murthy, Vinicius Ludwig, Andrei Gafita, Thomas A. Hope, Jeremie Calais","doi":"10.2967/jnumed.124.268818","DOIUrl":"https://doi.org/10.2967/jnumed.124.268818","url":null,"abstract":"<p>Prostate-specific membrane antigen (PSMA) PET is a well-established imaging tool for the evaluation of primary and recurrent prostate cancer (PCa). ¹⁷⁷Lu PSMA-targeted radiopharmaceutical therapy (RPT) enables direct delivery of β-radiation to PSMA-expressing PCa cells while minimizing damage to normal tissue. As PSMA RPT becomes more widely used, there is growing interest in evaluating the predictive and prognostic role of PSMA PET parameters to enable better patient selection and effectively monitor treatment response. The purpose of this paper is to review the role of PSMA PET parameters as biomarkers for PSMA RPT. Quantitative parameters on baseline PSMA PET can serve as prognostic biomarkers for overall survival and predictive biomarkers for prostate-specific antigen response. Alongside lesion-based assessments, changes in whole-body quantitative parameters from baseline to interim or end-of-treatment PSMA PET are prognostic for overall survival and progression-free survival in patients undergoing PSMA RPT. Changes in quantitative, whole-body PSMA PET parameters may better reflect changes in PCa following systemic therapy compared with individual lesion-based assessments. Further research is necessary in larger, prospective trials to characterize the role of PSMA PET parameters as prognostic biomarkers for progression-free survival and overall survival in metastatic castration-resistant PCa patients undergoing PSMA RPT.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Preclinical Evaluation of [64Cu]Cu-NOTA-ABDB6: A CD70 and Albumin Dual-Binding Tracer with Improved Pharmacokinetics","authors":"Xiaoyan Li, You Zhang, Jason C. Mixdorf, Qianyun Wu, Sophia J. Lee, Jonathan W. Engle, Todd E. Barnhart, Shannon C. Kenney, Lixin Rui, Weijun Wei, Weibo Cai","doi":"10.2967/jnumed.124.268835","DOIUrl":"https://doi.org/10.2967/jnumed.124.268835","url":null,"abstract":"<p>CD70 is an emerging biomarker for both solid tumors and hematologic malignancies, highlighting the urgent need for a molecular imaging tracer capable of visualizing CD70 with favorable pharmacokinetics. <strong>Methods:</strong> ABDB6 was prepared by fusing the albumin-binding domain ABD035 with the CD70-targeting single-domain antibody RCCB6, which we previously reported. The resulting ABDB6 was then conjugated to the bifunctional chelator <em>p</em>-SCN-NOTA and labeled with ⁶⁴Cu to produce [⁶⁴Cu]Cu-NOTA-ABDB6. Flow cytometry was used to screen 6 lymphoma cell lines with varying CD70 expression levels. Cell uptake and in vivo immuno-PET imaging studies were conducted to fully evaluate the pharmacokinetic properties and tumor-targeting efficacy of [⁶⁴Cu]Cu-NOTA-ABDB6. An ABDB6 blocking study was performed to validate the targeting specificity of [⁶⁴Cu]Cu-NOTA-ABDB6, followed by immunohistochemistry and fluorescent immunostaining studies to correlate tracer uptake with CD70 expression. <strong>Results:</strong> ⁶⁴Cu labeling of ABDB6 achieved a high radiochemical yield and specific activity. Significant CD70 expression was observed in 5 lymphoma cell lines (TMD8, HBL1, OCI-LY10, LCL-EBV, and type III latency Burkitt lymphoma [BL] cells) but not in type I latency BL cells, which served as the negative control. [⁶⁴Cu]Cu-NOTA-ABDB6 exhibited good affinity for CD70 protein at the nanomolar level (inhibitory concentration of 50%, 91.57 nM) and specificity in binding to human CD70. Immuno-PET imaging of [⁶⁴Cu]Cu-NOTA-ABDB6 demonstrated excellent tumor uptake and retention in various CD70-positive lymphoma models (TMD8, type III latency BL, and LCL-EBV), with the highest tumor uptake values recorded as 24.67 ± 1.36, 18.02 ± 4.29, and 14.68 ± 1.20 percentage injected dose per gram of tissue (%ID/g) at 48 h after injection, respectively. These tumor uptake values were significantly higher than that of the CD70-negative type I latency BL tumor, which had an uptake of 3.59 ± 0.28 %ID/g at the same scanning time point (<em>P</em> &lt; 0.05). In the TMD8 blocking group, tumor uptake was 5.99 ± 1.20 %ID/g at 48 h after injection, significantly lower than in the TMD8 control group (<em>P</em> &lt; 0.01). Both biodistribution and histology results corroborated these imaging findings. <strong>Conclusion:</strong> [⁶⁴Cu]Cu-NOTA-ABDB6 immuno-PET effectively visualized varying levels of CD70 in different lymphoma models. Its clinical potential may provide insights into CD70 expression in lymphoma patients.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517870","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":"IL13Rα2-Targeting Antibodies for Immuno-PET in Solid Malignancies","authors":"Leah Gajecki, Irina V. Lebedeva, Yu-Rou Liao, Daisy Ambriz, Lukas M. Carter, Melina Kumpf, Samantha Lovibond, Justin S. Hachey, Maya S. Graham, Michael Postow, Jason S. Lewis, David P. Andrew, Manuel Baca, Heiko Schöder, Steven M. Larson, Darren R. Veach, Simone Krebs","doi":"10.2967/jnumed.124.268762","DOIUrl":"https://doi.org/10.2967/jnumed.124.268762","url":null,"abstract":"<p>Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma and melanoma, with limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor delineation. In this study, we report the development of 5 novel IL13Rα2-targeted human monoclonal antibodies (mAbs) KLG-1–5; in subsequent in vitro and in vivo studies after radiolabeling with ⁸⁹Zr, we evaluate their performance to identify a lead candidate. <strong>Methods:</strong> Five novel human anti-IL13Rα2 mAbs KLG-1–5 were developed and in vitro binding properties and target specificity assessed. In vivo ⁸⁹Zr-immuno-PET using KLG-1–5 was conducted in a subcutaneous U-87 MG glioblastoma mouse model, and a mass dose titration study was conducted with lead candidate KLG-3. Ex vivo biodistribution results were used to derive prospective dosimetry of ¹⁷⁷Lu-labeled KLG-3. Targeting with KLG-3 was also verified in an A-375 melanoma model using the optimized conditions determined in the U-87 MG xenograft model. <strong>Results:</strong> In vitro studies confirmed target specificity and pico- to low nanomolar binding affinity. Immuno-PET studies with KLG-1–5 in U-87 MG xenografts demonstrated continuously increasing tumoral uptake with maximal uptake at 144 h after tracer injection, clearance of the unbound tracer from the blood pool, and little uptake in any other normal tissues, leading to high-contrast images. KLG-3 provided the highest tumoral uptake and tumor–to–normal tissue ratios and was chosen as the lead candidate, and further dose optimization with this antibody led to tumoral uptake of 97 ± 6 maximum percent of injected dose per gram at 144 h after tracer injection. Ex vivo biodistribution-derived prospective dosimetry for ¹⁷⁷Lu-labeled KLG-3 predicted a favorable therapeutic index, encouraging the development of IL13Rα2-targeted radioimmunotherapy. Of note, KLG-3 performed similarly well in a melanoma model, emphasizing the versatility of this antibody. <strong>Conclusion:</strong> Lead candidate anti-IL13Rα2 mAb KLG-3 validated highly specific target binding in human glioblastoma and melanoma models, resulting in high-contrast PET images with minimal accumulation in off-target healthy tissues. Prospective dosimetry of its ¹⁷⁷Lu-labeled counterpart suggested therapeutic efficacy at relatively low injected activities, supporting further pursuit of KLG-3 in future translational radioimmunotherapy applications.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462475","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":"Therapy-Related Myeloid Neoplasms After [177Lu]Lu-PSMA Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Case Series","authors":"Michal Eifer, Duncan E.K. Sutherland, Isaac Goncalves, James P. Buteau, Lewis Au, Arun A. Azad, Louise Emmett, Grace Kong, Louise Kostos, Aravind S. Ravi Kumar, Edmond M. Kwan, Elizabeth Medhurst, Shahneen Sandhu, Ben Tran, Alexander W. Wyatt, Michael S. Hofman","doi":"10.2967/jnumed.124.268640","DOIUrl":"https://doi.org/10.2967/jnumed.124.268640","url":null,"abstract":"<p>[¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA) therapy has a favorable toxicity profile in patients with metastatic castration-resistant prostate cancer (mCRPC). Therapy-related myeloid neoplasm (t-MN) has been described after [¹⁷⁷Lu]Lu-DOTATATE but has not, to our knowledge, yet been reported after [¹⁷⁷Lu]Lu-PSMA. This case series describes 5 patients with mCRPC who developed t-MN after [¹⁷⁷Lu]Lu-PSMA at our institution. <strong>Methods:</strong> In this single-center retrospective analysis, we reviewed all patients with mCRPC treated with [¹⁷⁷Lu]Lu-PSMA. Patients who developed biopsy-proven t-MN during or after [¹⁷⁷Lu]Lu-PSMA treatments are summarized with descriptive statistics. <strong>Results:</strong> From August 26, 2015, to December 31, 2022, 5 of 381 (1.3%) patients treated with [¹⁷⁷Lu]Lu-PSMA were subsequently diagnosed with t-MN. Their median age at cycle 1 (C1) was 78 y (range, 65–80 y). The median time from C1 to t-MN diagnosis was 33.6 mo (range, 6.0–58.8 mo). Previous treatments included docetaxel (<em>n</em> = 5), external-beam radiotherapy to metastases (<em>n</em> = 5), abiraterone (<em>n</em> = 4), enzalutamide (<em>n</em> = 3), and cabazitaxel (<em>n</em> = 3). On PSMA PET/CT, 4 (80%) patients had predominantly bone metastases and 1 (20%) had predominantly nodal metastases. They were treated with [¹⁷⁷Lu]Lu-PSMA-617 (<em>n</em> = 3) or [¹⁷⁷Lu]Lu-PSMA-I&amp;T (<em>n</em> = 2). A median of 7 cycles (range, 4–12 cycles) of [¹⁷⁷Lu]Lu-PSMA was administered, with a median total cumulative activity of 49.2 GBq (range, 31.3–79.0 GBq). Prostate-specific antigen reduction of at least 50% or at least 80% from baseline was seen in 5 (100%) and 4 (80%), respectively. All had prostate-specific antigen progression preceding t-MN diagnosis. t-MN diagnosis included myelodysplastic syndrome with single-lineage dysplasia (<em>n</em> = 2), myelodysplastic syndrome with excess blasts 1 (<em>n</em> = 1), acute promyelocytic leukemia (<em>n</em> = 1), and acute myeloid leukemia (<em>n</em> = 1). At t-MN diagnosis, all patients presented with at least grade 2 cytopenia, involving one or more blood cell lines. Marrow genetic analysis revealed unfavorable karyotypes or mutations in all patients. Most patients received supportive care after t-MN diagnosis. Survival was 8.1, 31.3, 43.0, 56.0, and 60.4 mo from C1 and 1.8, 2.1, 6.8, 10.3, and 12.4 mo from t-MN diagnosis. <strong>Conclusion:</strong> In the mCRPC population after chemotherapy, we describe a low incidence of t-MN after [¹⁷⁷Lu]Lu-PSMA therapy. Ongoing follow-up is necessary to further define the true incidence of t-MN or other unexpected delayed toxicities, particularly with earlier use of [¹⁷⁷Lu]Lu-PSMA in the disease course.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462482","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":"PSMA-Guided Metastasis-Directed Therapy for Oligometastatic Renal Cell Carcinoma: The Proof-of-Concept PEDESTAL Study","authors":"Cristian Udovicich, Mathias Bressel, Jamil Manji, Muhammad Ali, Lewis Au, Arun A. Azad, James P. Buteau, Sarat Chander, David Chang, Renu Eapen, Nathan Lawrentschuk, Sidney M. Levy, Daniel Moon, Declan G. Murphy, Marlon Perera, Mark Shaw, Lavinia Spain, Ben Tran, Michael S. Hofman, Shankar Siva","doi":"10.2967/jnumed.124.268639","DOIUrl":"https://doi.org/10.2967/jnumed.124.268639","url":null,"abstract":"<p>Metastasis-directed therapy (MDT) in oligometastatic renal cell carcinoma (RCC) is typically based on conventional imaging. Prostate-specific membrane antigen (PSMA) PET/CT has shown superiority over conventional imaging. Our objective was to perform a proof-of-concept study to evaluate the efficacy of PSMA-guided MDT in oligometastatic RCC. <strong>Methods:</strong> A PSMA PET/CT database was queried for oligometastatic RCC patients undergoing MDT from 2014 to 2020. The primary endpoint was progression-free survival. Secondary endpoints included freedom from local progression, freedom from change in systemic therapy strategy, and overall survival. <strong>Results:</strong> A search of 3,095 PSMA PET/CT scans identified 83 RCC patients and 34 receiving MDT to 60 sites. The median follow-up was 4.1 y. Six patients (18%) had synchronous metastatic disease. The median number of metastases was 1 (interquartile range, 1–2). Common sites included bone (19, 32%) and lung (19, 32%). Radiation therapy was delivered to 56 metastases (93%), including stereotactic ablative body and conventional radiotherapy (38 and 18 metastases, respectively), and 4 (7%) underwent surgery. One-, 3-, and 5-y freedom from local progression was 94% (95% CI, 85%–98%), 85% (95% CI, 69%–94%), and 85% (95% CI, 69%–94%), respectively. One-, 3-, and 5-y overall survival was 88% (95% CI, 71%–95%), 71% (95% CI, 52%–84%), and 64% (95% CI, 45%–79%), respectively. One-, 3-, and 5-y progression-free survival was 47% (95% CI, 30%–63%), 26% (95% CI, 13%–42%), and 8% (95% CI, 2%–22%), respectively. One-, 3-, and 5-y freedom from change in systemic therapy strategy was 76% (95% CI, 57%–87%), 65% (95% CI, 45%–79%), and 43% (95% CI, 19%–65%), respectively. <strong>Conclusion:</strong> In this proof-of-concept study, PSMA-guided MDT provided durable oncologic outcomes for oligometastatic RCC, even at 5 y. To our knowledge, this study had the first cohort uniformly undergoing PSMA-guided MDT and one of the longest follow-ups of MDT for oligometastatic RCC. With increasing availability, PSMA PET/CT can be rapidly instituted to select patients for MDT and improve outcomes for patients with oligometastatic RCC.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462472","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":"An International Study of Factors Affecting Variability of Dosimetry Calculations, Part 4: Impact of Fitting Functions in Estimated Absorbed Doses","authors":"Sara Kurkowska, Julia Brosch-Lenz, Yuni K. Dewaraja, Eric Frey, John Sunderland, Carlos Uribe","doi":"10.2967/jnumed.124.268612","DOIUrl":"https://doi.org/10.2967/jnumed.124.268612","url":null,"abstract":"<sec><st>Visual Abstract</st><p><fig loc=\"float\"><link locator=\"jnumed.124.268612absf1\"></fig></p></sec>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462480","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":"PET Imaging of PD-L1 Occupancy for Preclinical Assessment of the Efficacy of Combined Anti–PD-L1 Immunotherapy and Targeted Therapy","authors":"Céline Chevaleyre, Léa Zimmermann, Simon Specklin, Dimitri Kereselidze, Alizée Bouleau, Steven Dubois, Hélène Quelquejay, Bernard Maillère, Nicolas Tournier, Hervé Nozach, Charles Truillet","doi":"10.2967/jnumed.124.268586","DOIUrl":"https://doi.org/10.2967/jnumed.124.268586","url":null,"abstract":"<p>The development of resistance significantly hampers the efficacy of immunotherapies in cancer treatment. The combination of JQ1, a BRD4 protein inhibitor, and anti–programmed death ligand 1 (PD-L1) immunotherapies has a synergic therapeutic potential to treat solid tumors. This study aimed to evaluate the potential of immuno-PET imaging for measuring pharmacodynamic biomarkers in response to this combination therapy targeting PD-L1. <strong>Methods:</strong> We synthesized different radioligands derived from the anti–PD-L1 C4 antibody and a minibody targeting murine CD8α for immuno-PET imaging. We conducted experiments on human non–small cell lung cancer and mouse colorectal carcinoma animal models to assess the efficacy of JQ1 and avelumab treatment on PD-L1 expression and immune cell infiltration by immuno-PET imaging. Taking advantage of the unique properties of the C4-derived minibody, we measured PD-L1 occupancy in tumors after treatment. <strong>Results:</strong> JQ1 efficiently reduced PD-L1 extracellular expression across all tested cell lines in vitro and in vivo. Avelumab and JQ1 treatments alone or in combination led to significant tumor growth reduction in the immunocompetent murine colorectal carcinoma model, reducing mean tumor growth from 725% in the control group to 125% in the combination group. Treatments also significantly increased the survival of mice by 4–12 d compared with the control group. Although imaging CD8-positive T-cell infiltration did not predict tumoral response, imaging the unoccupied fraction of PD-L1 after treatment was predictive of tumor growth reduction and survival. <strong>Conclusion:</strong> Immuno-PET imaging with noncompetitive radioligands throughout the treatment course could improve the efficiency and support rationalization of the dosing regimen of immunotherapies.</p>","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462478","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}