The Journal of Nuclear Medicine最新文献

{"title":"First Total-Body Kinetics Study of 18F-Flurpiridaz in Healthy Volunteers at Rest and Feasibility of Simplified Quantitative Strategies.","authors":"Hao Song,Zhenyu Xiang,Yihan Wang,Jingxu Zhao,Yongpeng Wen,Zhixing Qin,Jia Gao,Zhifang Wu,Ping Wu,Sijin Li","doi":"10.2967/jnumed.125.270997","DOIUrl":"https://doi.org/10.2967/jnumed.125.270997","url":null,"abstract":"The multiorgan kinetic profile of 18F-flurpiridaz targeting mitochondrial complex I remains inadequately characterized. We aim to characterize preliminary total-body pharmacokinetics of 18F-flurpiridaz in healthy volunteers and evaluate shortened acquisition protocols for clinical translation. Methods: Twelve healthy volunteers were imaged with 18F-flurpiridaz during a 60-min dynamic total-body PET/CT scan on the uEXPLORER scanner at rest. Time-activity curves were derived from volumes of interest generated by an automated CT-based segmentation method applied to motion-corrected dynamic PET images, with manual delineation of the descending aorta, kidney, and breasts. The descending aorta served as the input function for most organs, whereas the pulmonary artery was used for the lungs. The 2-tissue irreversible (2T3K) and 2-tissue reversible (2T4K) compartment models incorporating blood volume and time-delay correction were compared using the Akaike information criterion (AIC). Simplified metrics of distribution volume (V T) from a Logan plot and SUVmean from truncated scans (10, 30, and 60 min) were correlated with the reference 60-min 2T4K V T Results: Four distinct kinetic patterns were observed across different organs. At 60 min, the 2T4K model demonstrated superior fitting performance (lower AIC) in 15 of 18 targeted regions. The 2T3K model exhibited lower AIC in the heart, brain, and kidneys at 10 min. In the thyroid and spinal cord, the optimal model shifted from the 2T3K model at 60 min to the 2T4K model at 10 min. Logan V T from 30-min (r = 0.974) and 60-min (r = 0.979) scans strongly correlated with reference V T Notably, SUVmean around 10-min postinjection also showed strong correlation with reference V T (r = 0.834-0.909), only slightly lower than that observed in the optimal 25-30-min window (r = 0.922; all P < 0.0001). Conclusion: This total-body kinetic atlas of 18F-flurpiridaz supports the use of the 2T4K model for multiorgan quantification, time-dependent model preference, and the feasibility of ultrashort imaging strategies for clinical mitochondrial complex I assessment, establishing a foundation for future applications in oncology (e.g., metabolism evaluation), neurology (e.g., mitochondrial mapping), and integrated cardio-oncology diagnostics.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599214","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":"Dosimetry Analysis of 177Lu-PSMA-I&T in Patients with Low-Volume Oligometastatic Hormone-Sensitive Prostate Cancer: A Secondary Analysis of the LUNAR Trial.","authors":"Zachary Ells,Catherine Meyer,Koichiro Kimura,Holly Wilhalme,Minsong Cao,Vinicius B Ludwig,Lena M Unterrainer,David Sennung,Rejah Nabong,Carol Felix,Luca F Valle,Anthony Daley,Johannes Czernin,Magnus Dahlbom,Amar U Kishan,Jeremie Calais","doi":"10.2967/jnumed.125.271467","DOIUrl":"https://doi.org/10.2967/jnumed.125.271467","url":null,"abstract":"The phase 2 LUNAR trial randomized (1:1) patients with oligorecurrent hormone-sensitive prostate cancer to neoadjuvant [177Lu]Lu-PSMA-I&T (2 cycles, 6.8 GBq) followed by stereotactic body radiotherapy (SBRT) versus SBRT alone. [177Lu]Lu-PSMA-I&T before SBRT was well tolerated and significantly improved PSMA PET/CT-based progression-free survival compared with SBRT alone. Here, we report the estimated absorbed doses (AD) of [177Lu]Lu-PSMA-I&T to organs at risk and lesions. Methods: This analysis was conducted on all 45 patients randomized to the investigational arm. Quantitative SPECT/CT images were acquired at 4, 24, and 72-96 h postinjection of cycle 1. Kidneys, salivary and lacrimal glands, and liver were delineated with deep learning-assisted segmentation, whereas lumbar vertebrae were manually segmented as a surrogate for bone marrow. Planned target volumes were transferred from the SBRT plans to the SPECT/CT series. Registration between time points was manually verified for each segmentation. ADs were estimated using a multiple-time-point voxel-based schema. Time-activity data were fit using a monoexponential function. Partial-volume effects were corrected using volume-specific phantom-based recovery coefficients. Results: In the 45 patients included, the median prostate-specific antigen was 1.10 ng/mL (range, 0.16-14.70 ng/mL). In total, 123 lesions total were identified, with a median per patient of 2 (range, 1-9). Median whole-body total tumor volume was 14.5 cm3 (range, 1.9-145.9 cm3). Median SUVmax on baseline PSMA PET/CT and 24-h SPECT/CT was 3.49 (range, 0.59-45.30) and 0.72 (range, 0.02-34.24), respectively. The AD to the kidneys, parotids, submandibulars, lacrimals, liver, and bone marrow were 0.35 ± 0.10, 0.20 ± 0.10, 0.24 ± 0.10, 0.70 ± 0.49, 0.03 ± 0.01, and 0.005 ± 0.002 Gy/GBq, respectively. The mean dose to bone (n = 38), lymph node (n = 82), and soft tissue (n = 3) lesions were 0.19 ± 0.42, 0.46 ± 0.81, and 0.30 ± 0.38 Gy/GBq, respectively. Conclusion: The ADs from [177Lu]Lu-PSMA-I&T to organs at risk were consistent with prior reports, supporting the safety in patients with oligorecurrent hormone-sensitive prostate cancer. There was substantial heterogeneity in lesion AD estimates on both inter- and intrapatient levels. Because of the limited spatial resolution of SPECT, partial-volume effects can underestimate the AD in small volumes. Nevertheless, 2 neoadjuvant cycles of [177Lu]Lu-PSMA-I&T before SBRT prolonged progression-free survival, consistent with effective treatment of occult disease beyond imaging detectability.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599215","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":"Whole-Body PET and the Brain-Heart Axis: Toward Sex- and Gender-Sensitive Neurocardiovascular Imaging.","authors":"Federico Caobelli","doi":"10.2967/jnumed.126.272293","DOIUrl":"https://doi.org/10.2967/jnumed.126.272293","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599520","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":"Longitudinal Evaluation of 18F-MK-6240 Along the Alzheimer Disease Continuum.","authors":"Anna O Giarratana,Erin Jonaitis,Robert J Przybelski,Karly Cody,Tobey J Betthauser,Robert Cadman,Sara Frost Alberson,Bradley T Christian,Sterling C Johnson","doi":"10.2967/jnumed.125.271127","DOIUrl":"https://doi.org/10.2967/jnumed.125.271127","url":null,"abstract":"Understanding the rate of tau accumulation is critical for staging Alzheimer disease (AD), monitoring its progression, and informing clinical trial design. Although PET imaging with 18F-MK-6240, also known as florquinitau, can track tau pathology, longitudinal data remain limited. We evaluated longitudinal tau changes using 18F-MK-6240 PET across cognitive stages and analyzed regional rates of change with the goal of informing future clinical trial outcome measures. Methods: In this observational study, 27 participants with varying cognitive statuses (cognitively unimpaired [CU], mild cognitive impairment [MCI], and AD) underwent 18F-MK-6240 PET at baseline and at 6, 12, and 24 mo (or at 18 and 30 mo during the COVID-19 pandemic). Amyloid positivity at baseline was determined with 11C-labeled Pittsburgh compound B PET. Tau PET data were analyzed as SUV ratios (SUVRs) in regions of interest (ROIs) corresponding to Braak staging as well as the inferior temporal gyrus and 2 composite ROIs (metatemporal composite [MTC]) and an early tau composite. Annualized SUVR changes were compared across groups and correlated with cognitive scores (Mini-Mental State Examination, Clinical Dementia Rating Scale, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale) using the Kruskal-Wallis test. Correlations between the change in SUVR and cognitive outcomes were estimated using Spearman ρ. Results: Baseline 18F-MK-6240 PET showed a minimal signal in CU participants, localized signal to the medial temporal lobe in participants with MCI, and a signal spanning the inferolateral temporal lobe and extending posteriorly along the ventral cortex in participants with AD. Longitudinal analysis showed that the annualized percent change in tau deposition in the MTC was 0.17% ± 4.16, 5.77% ± 2.97, and 4.31% ± 5.84 in the CU, MCI, and AD groups, respectively (P = 0.075). The change in tau deposition was 0.00 ± 0.05, 0.10 ± 0.07, and 0.12 ± 0.16 in the CU, MCI, and AD groups, respectively (P = 0.039). Tau accumulation correlated with a decline on the Alzheimer Disease Assessment Scale-Cognitive Subscale (ρ = 0.43, P < 0.05). Conclusion: 18F-MK-6240 PET tracked tau accumulation over time and provided preliminary evidence that these changes correlate with cognitive decline, supporting its utility for longitudinal AD studies and trial design, with MTC emerging as a promising ROI for clinical trials.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599522","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":"Detection of Focal Lesions in Epilepsy with [18F]UCB-H Synaptic Vesicle Protein 2A PET Imaging.","authors":"Vanessa Pakula,Julia S Dorneich,Lukas Frontzkowski,Laura M Bartos,Nicholas Fearns,Sebastian N Roemer-Cassiano,Simon Lindner,Andreas Zwergal,Elisabeth Kaufmann,Günter Höglinger,Nicolai Franzmeier,Rudolf A Werner,Christian Vollmar,Jan Rémi,Matthias Brendel,Johannes Gnörich","doi":"10.2967/jnumed.125.271505","DOIUrl":"https://doi.org/10.2967/jnumed.125.271505","url":null,"abstract":"Synaptic vesicle protein 2A (SV2A) is a universal marker of synaptic density. Recent advances in SV2A-targeted radiotracers have opened new windows into synaptic imaging. In focal epilepsy, synaptic dysfunction is a central pathologic feature. Unlike [18F]FDG PET, which reflects neuronal metabolism only indirectly, SV2A PET allows for direct quantification of synaptic density. We therefore evaluated [18F]UCB-H SV2A PET in comparison to [18F]FDG PET in patients with pharmacoresistant, unilateral focal epilepsy, aiming to assess its complementary value to established metabolic imaging. Methods: In total, 29 patients with unilateral focal epilepsy underwent both dynamic [18F]UCB-H PET (0-60 min) and static [18F]FDG PET (30-50 min) imaging. Eight patients were treated with the SV2A-binding medications levetiracetam or brivaracetam. [18F]UCB-H PET time-activity curves were extracted from 35 frames across cortical and subcortical regions, and Pearson correlation coefficients with [18F]FDG uptake were calculated for each frame to identify the most suitable imaging windows. Voxelwise percentage differences between epileptogenic and contralateral healthy hemispheres were computed to determine lesion severity and volume. Finally, we evaluated gaussian smoothing kernels for minimizing background noise while preserving contrast during lesion detection. Results: Treatment with SV2A-binding medications reduced late-phase [18F]UCB-H binding up to 75% compared with untreated individuals, demonstrating high target specificity. Framewise correlation analysis in unaffected contralateral hemispheres revealed significant associations between [18F]UCB-H and [18F]FDG uptake within the 0-10-min and 30-60-min postinjection intervals. These time windows were therefore selected for early- and late-phase analyses, respectively. Within epileptogenic foci, SV2A PET lesion severity correlated with [18F]FDG uptake for both early-phase (r = 0.61, P = 0.0042) and late-phase (r = 0.63, P = 0.0027) imaging. However, only early-phase SV2A PET lesion volume correlated with [18F]FDG lesion volume (r = 0.70, P = 0.0004), whereas late-phase SV2A PET volume did not. In line, [18F]FDG and early-phase [18F]UCB-H PET visually showed broad hypometabolic and hypoperfused areas around the epileptogenic zone, whereas late-phase [18F]UCB-H PET yielded sharper, high-contrast delineation of synaptic abnormalities. Conclusion: Dual-phase [18F]UCB-H PET provides complementary perfusion-like and synaptic information in focal epilepsy and shows spatial correspondence with [18F]FDG PET while offering more spatially confined synaptic signal changes.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"120 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599320","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":"Pulling Together: A 5-Year Plan to Improve Theranostic Outcomes by Improving the Accuracy of Dosimetry-An FNIH Joint Academic, Clinical, and Industrial Collaboration.","authors":"Dale L Bailey,John C Dickson,Suzanne E Lapi,Carlos Uribe,Clarita Saldarriaga Vargas,Price Jackson,Caroline Stokke,Julia Brosch-Lenz,Althea Lang,Stephen A Graves,John J Sunderland","doi":"10.2967/jnumed.125.271665","DOIUrl":"https://doi.org/10.2967/jnumed.125.271665","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"122 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599519","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":"Translation of Intraoperative Molecular Imaging for Clinical Use.","authors":"Lauren T Rosenblum,Arjun Pant,Catherine Yip,Gary Kohanbash,W Barry Edwards,Marcus M Malek","doi":"10.2967/jnumed.124.268773","DOIUrl":"https://doi.org/10.2967/jnumed.124.268773","url":null,"abstract":"Intraoperative molecular imaging (IMI) is an evolving tool that enables targeted real-time visualization and delineation of tissue during surgery. IMI tracers can be fluorescent, radioactive, or dual-labeled. Their integration into the intraoperative setting is supported by several clinical trials, which led to Food and Drug Administration approval for a variety of these agents. Fluorescent tracers enable excellent spatial visualization, whereas radiotracers enable deep tissue detection, and dual-labeled tracers provide both. Novel activatable tracers that leverage properties of the tumor microenvironment are also being developed. Advances in imaging devices now permit IMI usage across diverse platforms, including minimally invasive surgery. Despite the limitations of autofluorescence, false-positive signals, and heterogeneity, the use of IMI continues to broaden in oncologic and nononcologic applications, driven by demonstrated improvements in surgical outcomes. In this review, we highlight the translation of IMI through clinical trials and future directions in IMI-guided surgery.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599218","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":"Theranostics Explained: A Personalized Approach to Cancer Care.","authors":"Alice F Viana,Elisa Cannarozzo","doi":"10.2967/jnumed.125.271895","DOIUrl":"https://doi.org/10.2967/jnumed.125.271895","url":null,"abstract":"","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"421 1","pages":"494-495"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147585628","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":"Improving the Somatostatin Receptor Status Assessment for Personalized and Precise Management of Neuroendocrine Neoplasms with the Use of a 99mTc-Radiolabeled Somatostatin Receptor Antagonist: The Final Results of the ERA PerMed TECANT Clinical Trial.","authors":"Alicja Hubalewska-Dydejczyk,Clemens Decristoforo,Renata Mikolajczak,Petra Kolenc,Marta Opalinska,Piotr Garnuszek,Konrad Skorkiewicz,Bogusław Glowa,Malgorzata Trofimiuk-Muldner,Andrej Studen,Urban Simoncic,Christine Rangger,Gianpaolo di Santo,Melpomeni Fani,Irene Virgolini,Luka Lezaic","doi":"10.2967/jnumed.125.270347","DOIUrl":"https://doi.org/10.2967/jnumed.125.270347","url":null,"abstract":"Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms in which an adequate expression of a somatostatin receptor (SSTR) serves as a target for imaging and therapy, typically using SSTR agonists. In the past decade, research in the field of NENs has focused on SSTR antagonists because of their higher and more sustained binding to a target, which may expand current diagnostic and therapeutic options, especially in patients with lower SSTR expression. The aim of this study was to perform a first-in-human injection of a novel 99mTc-labeled SSTR type 2 antagonist to establish safety, pharmacokinetics, and first assessment of SSTR status in patients with NENs through a qualitative and quantitative comparison with 68Ga-SSTR PET as a reference standard. Methods: Patients with metastatic grade 1 or 2 NENs and proven SSTR expression in primary and metastatic lesions on SSTR PET were imaged after a first-in-human injection of [99mTc]Tc-TECANT1. Assessment of safety, pharmacokinetics, and dosimetry was performed as a primary endpoint, with comparison of diagnostic performance and quantification of uptake to SSTR PET as a secondary endpoint. Results: Ten patients were enrolled. [99mTc]Tc-TECANT1 was found to be safe, with favorable pharmacokinetics and dosimetry (average total body effective dose of 3.3 ± 0.7 mSv). The diagnostic performance in comparison to that of SSTR PET was found to be superior, with a comparable or a higher number of detected lesions and superior target-to-background contrast (a factor of 2 and above for lesions with the highest uptake). Conclusion: [99mTc]Tc-TECANT1 appears to be a safe and widely utilizable radiopharmaceutical for the assessment of SSTR expression status in NENs. Validation of results in a larger cohort is warranted.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518445","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":"Validation of Folate Receptor-α Selectivity of 6S-5-Methyltetrahydrofolate-Based Radioconjugates: A Prerequisite for Therapeutic Application?","authors":"Ana Katrina Mapanao,Benjamin D Hunkeler,Giovanni Marzaro,Christian Vaccarin,Marco M Bühler,Roger Schibli,Niels J Rupp,Cristina Müller","doi":"10.2967/jnumed.125.271209","DOIUrl":"https://doi.org/10.2967/jnumed.125.271209","url":null,"abstract":"The development of folic acid-based radioconjugates has been proposed for imaging and targeted radionuclide therapy of folate receptor-α (FRα)-positive cancer. Although folic acid binds both the tumor-associated FRα and the folate receptor-β (FRβ) expressed on certain blood cells, 6S-5-methyltetrahydrofolate (6S-5-MTHF) was reported to exhibit higher affinity for FRα. The aim of this study was, therefore, to investigate whether previously developed 6S-5-MTHF-based radioconjugates would preferentially bind to FRα. Methods: The 6R- and 6S-5-MTHF-based folate radioconjugates [177Lu]Lu-RedFol-1, [177Lu]Lu-RedFol-3, [177Lu]Lu-RedFol-24, and [177Lu]Lu-RedFol-25 were evaluated in vitro using transfected Chinese hamster ovary cells to assess their cell uptake and binding affinity to FRα expressed on RT16 cells and to FRβ expressed on D4 cells. Biodistribution and SPECT/CT imaging studies of the 5-MTHF-based radioconjugates were performed in a mouse model bearing both RT16 and D4 xenografts. Immunohistochemical staining was performed on selected patient-derived tissue sections of high-grade serous ovarian carcinoma, kidney, and bone marrow to provide a representative overview of FRα and FRβ expression. Results: The uptake and receptor binding affinity of 6R-5-MTHF-based radioconjugates were in the same range for RT16 and D4 cells, indicating comparable binding to the FRα and FRβ. The 6S-5-MTHF-based radioconjugates showed a 4-6-fold higher uptake in RT16 cells than in D4 cells, which can be ascribed to the 9-29-fold increased binding affinity to FRα than to FRβ. In vivo, the uptake of 6R-5-MTHF-based radioconjugates in RT16 and D4 xenografts reached 55%-73% IA/g and 25%-44% IA/g at 24 h after injection, respectively. The accumulation of 6S-5-MTHF-based radioconjugates in RT16 xenografts was 74%-100% IA/g, which was 9-21-fold higher than the 4%-10% IA/g uptake observed in D4 xenografts. Immunohistochemistry data confirmed high FRα expression in human ovarian cancer tissue sample and the presence of FRα in renal proximal tubules. In contrast, FRα was absent in human bone marrow, where FRβ was substantially expressed. Conclusion: This study confirmed that the use of 6S-5-MTHF-based radioconjugates can enable selective targeting of FRα. The high expression levels of FRα in ovarian cancer but absence in the bone marrow of human tissue samples infer therapeutic and safety benefits of using FRα-selective folate radioconjugates. Measures to reduce renal retention of 6S-5-MTHF radioconjugates may, however, still be necessary.","PeriodicalId":22820,"journal":{"name":"The Journal of Nuclear Medicine","volume":"219 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518527","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}