Steven Blinka, Risa L Wong, Sarah K Holt, Ethan Lo, Heather H Cheng, Nathan Conrad, Hannah Loesch, Andrea E Toulouse, Michael Lai, Andrew C Hsieh, Petros Grivas, Todd Yezefski, Jonathan L Wright, Michael T Schweizer, Robert B Montgomery, Delphine L Chen, Jing Zeng, Daniel W Lin, Evan Y Yu
{"title":"Results from a prospective registry of <sup>18</sup>F-Fluciclovine PET/CT use in prostate cancer management: a cautionary lesson for implementation of PSMA PET.","authors":"Steven Blinka, Risa L Wong, Sarah K Holt, Ethan Lo, Heather H Cheng, Nathan Conrad, Hannah Loesch, Andrea E Toulouse, Michael Lai, Andrew C Hsieh, Petros Grivas, Todd Yezefski, Jonathan L Wright, Michael T Schweizer, Robert B Montgomery, Delphine L Chen, Jing Zeng, Daniel W Lin, Evan Y Yu","doi":"10.62347/IAWB9145","DOIUrl":"10.62347/IAWB9145","url":null,"abstract":"<p><strong>Background: </strong><sup>18</sup>F-Fluciclovine positron emission tomography (PET) was FDA-approved in the U.S. in 2016 and was the most sensitive imaging modality for prostate cancer (PC) until the approval of prostate-specific membrane antigen (PSMA) PET in 2020. However, providers' reasons for ordering <sup>18</sup>F-Fluciclovine PET/CT (FluPET) in practice and impact on patient care remain poorly defined. This prospective registry at a tertiary academic center describes patterns of FluPET use and outcomes prior to the FDA approval of PSMA PET in December 2020.</p><p><strong>Methods: </strong>Providers ordering FluPET for patients with PC were surveyed before, ≤2 weeks after, and ≥1 year after imaging to assess reasons for obtaining FluPET, projected treatment plan, changes in plan due to FluPET findings, and toxicity attributable to the change in treatment plan. Baseline patient characteristics, FluPET results, and longitudinal outcomes were collected.</p><p><strong>Results: </strong>Between 12/2018-09/2021, 62 patients with localized PC (8.1%), biochemical recurrence (BCR; 80.6%), non-metastatic castration-resistant PC (CRPC) (3.2%), metastatic castration-sensitive PC (3.2%), or metastatic CRPC (4.8%) were enrolled and underwent FluPET. Most scans (90.3%) were performed prior to the FDA approval of PSMA PET 12/2020. FluPET was most often obtained to guide local salvage or metastasis-directed therapies (90.3%); other reasons (non-exclusive) were initial staging (9.6%) or clarifying equivocal lesions from other imaging (9.6%). FluPET detected ≥1 PC lesion in 74.2% of patients. After FluPET, 48.4% of providers reported changing treatment plans, which was more likely when FluPET was positive (60.9% vs 12.5%, P<0.001), and often involved initiation of systemic therapy (19.4%). Treatment changes were reported in 57% of patients with BCR1 and 48.2% of patients with BCR2. In contrast, only 20% of patients with distant metastatic disease had a change in treatment. Among patients in the BCR1 and BCR2 cohort, treatment plan changes were associated with a median time to next treatment that was not reached after a median follow-up of 67.6 months. There was no statistically significant difference in overall survival between patients with biochemical recurrence (BCR) who did and did not have a treatment plan change. A year after FluPET, reported potential toxicities from treatment plan changes were minimal.</p><p><strong>Conclusion: </strong>FluPET was utilized across the disease spectrum of PC, primarily to guide local salvage or metastasis-directed therapies, given its improved sensitivity for detecting prostate bed recurrence due to the slow physiologic excretion of <sup>18</sup>F-fluciclovine. Notably, a positive FluPET frequently prompted initiation of systemic therapy; however, the clinical benefit of such management remains uncertain. Moreover, providers often selected multiple, sometimes conflicting, treatment plans following FluPET, re","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 6","pages":"262-271"},"PeriodicalIF":1.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016893","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}
Jaskeerat Gujral, Om H Gandhi, Amir A Amanullah, Shashi B Singh, Cyrus Ayubcha, Thomas J Werner, Mona-Elisabeth Revheim, Abass Alavi
{"title":"Somatostatin receptor PET-guided treatment and artificial intelligence applications in meningioma: a comprehensive review.","authors":"Jaskeerat Gujral, Om H Gandhi, Amir A Amanullah, Shashi B Singh, Cyrus Ayubcha, Thomas J Werner, Mona-Elisabeth Revheim, Abass Alavi","doi":"10.62347/LYAT6783","DOIUrl":"10.62347/LYAT6783","url":null,"abstract":"<p><p>Meningiomas are the most common primary intracranial tumors, with treatment involving resection and radiation therapy. However, therapeutic options are limited for recurrent or progressive disease, particularly in higher World Health Organization (WHO) grade tumors. Somatostatin receptor (SSTR) expression in meningiomas has opened new therapeutic opportunities as the differential SSTR2 overexpression permits molecular targeting using radiolabeled somatostatin analogs. PRRT offers promising therapeutic efficacy in select meningioma patients, with clinical responses strongly correlated to WHO tumor grade and SSTR expression levels. Combining SSTR PET imaging, to evaluate receptor density, with radiomic analysis can reveal tumor heterogeneity patterns and quantitative imaging features that can guide clinical decision-making and monitor treatment response. Integrating machine learning and artificial intelligence (AI) into clinical workflows offer novel approaches to apply quantitative SUV parameters, image texture features, and histopathologic data in order to identify patients with WHO grade II and III meningiomas at greater risk of tumor recurrence. Given the heterogeneity in imaging and treatment protocols across institutions and the limited number of PRRT-treated meningioma cohorts, future research should prioritize prospective, multicenter studies that integrate histologic and molecular imaging data to refine patient selection strategies and establish PRRT's role within personalized, precision cancer treatment paradigms.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 6","pages":"223-235"},"PeriodicalIF":1.8,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016998","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":"From lutetium to terbium: a new era in PSMA-targeted radioligand therapy for mCRPC patients.","authors":"Steven H Liang","doi":"10.62347/JAXA6254","DOIUrl":"10.62347/JAXA6254","url":null,"abstract":"<p><p>Terbium-161 (<sup>161</sup>Tb) is emerging as a promising theranostic radionuclide for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC). Compared with lutetium-177 (<sup>177</sup>Lu), <sup>161</sup>Tb emits additional high-linear energy transfer Auger and internal conversion electrons, enabling superior tumor cell kill in micrometastatic disease. Early clinical studies demonstrate favorable safety, dosimetry, and efficacy profiles for <sup>161</sup>Tb-labeled PSMA ligands. Ongoing trials and production advancements are critical to fully realizing the therapeutic potential of <sup>161</sup>Tb-based RLT.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 5","pages":"219-222"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585942","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}
Monica Cheng, Umar Mahmood, Nathaniel D Mercaldo, Shadi A Esfahani, Thomas Ng, Xin Gao, Jason A Efstathiou, Pedram Heidari
{"title":"Molecular tumor volume on PSMA PET/CT is an independent imaging biomarker associated with progression-free survival in patients with oligorecurrent prostate cancer.","authors":"Monica Cheng, Umar Mahmood, Nathaniel D Mercaldo, Shadi A Esfahani, Thomas Ng, Xin Gao, Jason A Efstathiou, Pedram Heidari","doi":"10.62347/NCJF9597","DOIUrl":"10.62347/NCJF9597","url":null,"abstract":"<p><p>The purpose of this study is to evaluate the PSMA PET imaging parameters in association with outcomes among patients with oligorecurrent prostate cancer. This retrospective single-center study included 101 patients (median age 71; interquartile range 65-75) with biochemically recurrent prostate cancer who underwent PSMA PET between May 2021 and May 2022, revealing 5 or fewer sites of metastases (oligometastatic disease). Multiple variables including maximum standardized uptake value (SUV<sub>max</sub>), mean standardized uptake value (SUV<sub>mean</sub>), and molecular tumor volume (MTV) were measured and analyzed on a per-patient basis, along with total MTV and molecular tumor burden (MTB). Multivariable Cox proportional-hazards regression models were used to identify factors associated with progression-free survival (PFS). PSMA PET revealed a total of 216 lesions across all patients, of which 134 (62.0%) involved the lymph nodes and 56 (25.9%) involved the bone. A total of 61 (60.4%) patients received combined metastasis-directed and hormone therapy, and 40 (39.6%) received hormone therapy only. The median subsequent follow-up from PSMA PET detection of oligorecurrent disease was 18.2 months (IQR 10.3-25.0). MTV on PSMA PET was associated with worse PFS (hazard ratio: 1.05, 95% CI 1.00-1.11; P = 0.04). Molecular tumor volume on PSMA PET is associated with worse clinical outcomes in patients with oligorecurrent prostate cancer.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 5","pages":"193-199"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585939","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":"PARP-targeted molecular imaging for noninvasive diagnosis and surgical guidance in basal cell carcinoma.","authors":"Steven H Liang","doi":"10.62347/BEJG4271","DOIUrl":"10.62347/BEJG4271","url":null,"abstract":"<p><p>Poly(ADP-Ribose) Polymerase 1 (PARP1) is a key DNA repair enzyme and therapeutic target in cancer, with overexpression observed in several cancers, including basal cell carcinoma (BCC). Conventional diagnostic methods for BCC lack specificity and are invasive, highlighting the need for noninvasive alternatives. PARP-targeted molecular imaging, particularly with fluorescence probes, has shown strong potential for tumor detection and real-time visualization. PARPi-FL, a fluorescent derivative of Olaparib, enables rapid, specific, and high-contrast imaging of BCC in preclinical and <i>ex vivo</i> human studies. Optimized application protocols confirm its safety and translational promise for noninvasive diagnosis and image-guided surgery.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 5","pages":"208-211"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585934","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":"Visualizing T-cell activation: PET imaging of CXCL9 as a window into the tumor immune response.","authors":"Jimmy S Patel, Runhong Li, Steven H Liang","doi":"10.62347/KSFZ9854","DOIUrl":"10.62347/KSFZ9854","url":null,"abstract":"<p><p>T-cell activation within the tumor microenvironment is a key determinant of response to immunotherapy, yet current biomarkers fail to capture its spatial and temporal dynamics. Traditional assays such as PD-L1 immunohistochemistry, tumor mutational analysis, and circulating cytokine profiling offer static or systemic snapshots that inadequately reflect localized immune engagement. Positron emission tomography (PET) provides a unique opportunity to visualize these processes <i>in vivo</i>. Among emerging tracers, CXCL9-targeted imaging stands out as a promising approach to quantify IFNγ-driven T-cell activation and recruitment. Jacobson <i>et al</i>. report the development of [<sup>18</sup>F]F-h2A12, a high-affinity nanobody PET tracer specific for CXCL9. Preclinical studies demonstrate robust uptake in CXCL9-expressing tumors, close correlation with intratumoral immune activation, and clear distinction from blood-based biomarkers. Compared with existing immune PET tracers that target cytotoxic enzymes, soluble cytokines, or surface activation markers, CXCL9 imaging offers an advantageous balance of specificity, localization, and functional relevance. By visualizing the chemokine gradients that govern T-cell trafficking, CXCL9 PET could serve as an early, noninvasive biomarker of immunotherapy response and a powerful tool for guiding adaptive treatment strategies.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 5","pages":"212-214"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585956","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}
Jian Rong, Chunyu Zhao, Ahmad F Chaudhary, Jiahui Chen, Yinlong Li, Xin Zhou, Zhendong Song, Zhenkun Sun, Yabiao Gao, Siyan Feng, Taoqian Zhao, Qi-Long Hu, Chongjiao Li, Achi Haider, Jimmy Patel, Chongzhao Ran, Hongjie Yuan, Steven H Liang
{"title":"Radiosynthesis and evaluation of an <sup>18</sup>F-labeled radioligand for imaging metabotropic glutamate receptor 3 with positron emission tomography.","authors":"Jian Rong, Chunyu Zhao, Ahmad F Chaudhary, Jiahui Chen, Yinlong Li, Xin Zhou, Zhendong Song, Zhenkun Sun, Yabiao Gao, Siyan Feng, Taoqian Zhao, Qi-Long Hu, Chongjiao Li, Achi Haider, Jimmy Patel, Chongzhao Ran, Hongjie Yuan, Steven H Liang","doi":"10.62347/MHBJ1846","DOIUrl":"10.62347/MHBJ1846","url":null,"abstract":"<p><p>The metabotropic glutamate receptor 3 (mGluR3) is a G-protein-coupled receptor (GPCR) involved in modulating glutamatergic neurotransmission and maintaining neural homeostasis. By inhibiting adenylyl cyclase activity, mGluR3 negatively modulates the activity of adenylyl cyclase via Gi/o protein coupling, reducing cyclic AMP (cAMP) levels and modulating downstream signaling pathways. Dysfunction of mGluR3 is associated with a range of neurological and psychiatric disorders, including depression, autism, cognitive impairment, bipolar affective disorder, schizophrenia, and neurodegenerative diseases. Despite its therapeutic relevance, no selective mGluR3 positron emission tomography (PET) radioligand is currently available to image this target <i>in vivo</i>. In this study, we report the radiosynthesis and preclinical evaluation of [<sup>18</sup>F]VU6010572 - a novel PET tracer based on a therapeutical drug candidate. VU6010572 exhibits potent binding affinity (IC<sub>50</sub> = 39.9 nM) and exceptional selectivity (>100-fold over other mGluR subtypes). Radiolabeling with fluorine-18 yielded [<sup>18</sup>F]VU6010572 with high radiochemical yield (48%, decay-corrected) and molar activity (59 GBq/µmol). While <i>in vitro</i> autoradiography demonstrated heterogeneous brain distribution, dynamic PET imaging in rodents revealed reasonable brain uptake <i>in vivo</i> yet modest binding specificity and rapid brain washout. While these findings support the potential of [<sup>18</sup>F]VU6010572 as a lead structure, further medicinal chemistry optimization is warranted to enhance the metabolic and pharmacokinetic properties.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 5","pages":"173-182"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585949","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":"DLL3-targeted immunoPET and radioimmunotherapy ligands.","authors":"Steven H Liang","doi":"10.62347/MRZS8767","DOIUrl":"10.62347/MRZS8767","url":null,"abstract":"<p><p>DLL3 is overexpressed on the cell surface of NENs, such as SCLC and NEPC, but notably restricted to cytoplasm with low expression levels in normal adult human tissues. Several radioligands have been developed by targeting DLL3 for immunoPET or radioimmunotherapy use. These ligands hold great promise for mapping the heterogeneous DLL3 expression in neuroendocrine tumors and guiding the DLL3-directed therapeutic strategies.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 5","pages":"215-218"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585894","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":"Performance of PRIMARY Score based on PSMA-PET imaging in suspected prostate cancer patients with different PSA ranges: a retrospective study.","authors":"Fuhao Zhang, Xiang Li, Jingliang Zhang, Zhiyong Quan, Zefei Zhang, Tingting Han, Xiaoli Meng, Lingyu Ma, Xuebing Yu, Weijun Qin, Fei Kang","doi":"10.62347/MKPM5648","DOIUrl":"10.62347/MKPM5648","url":null,"abstract":"<p><strong>Purpose: </strong>To refine the optimal PRIMARY score thresholds across different PSA ranges, enhancing diagnostic accuracy for clinically significant prostate cancer (csPCa).</p><p><strong>Methods: </strong>The study retrospectively analyzed 373 patients who underwent PSMA PET/CT scans for suspected csPCa between June 2021 and December 2023. The diagnostic efficacy of PRIMARY score was independently assessed using 68Ga-PSMA PET/CT. Receiver-operating characteristic curve analysis was used to estimate the diagnostic performance. The diagnostic efficacy of the PRIMARY score with different thresholds in different PSA ranges was also calculated and compared.</p><p><strong>Results: </strong>The PRIMARY score maintains high diagnostic accuracy either in group of PSA ≤ 20 ng/mL or PSA > 20 ng/mL, with an AUC exceeding 0.8 at appropriate thresholds. Notably, in patients with PSA > 20 ng/mL, a PRIMARY score threshold of 4 demonstrated enhanced diagnostic accuracy compared to a threshold of 3, significantly improving specificity from 70.6% to 91.2% while maintaining high sensitivity (from 99.2% to 98.4%). Consequently, 91.2% (31/34) patients could avoid unnecessary biopsies, at the expense of missing 1.6% (2/125) of csPCa cases.</p><p><strong>Conclusion: </strong>Across different PSA ranges, the PRIMARY score based on <sup>68</sup>Ga-PSMA PET/CT imaging is useful in the diagnosis of csPCa. A threshold of 3 for PSA ≤ 20 ng/mL and a threshold of 4 for 20 ng/mL < PSA ≤ 50 ng/mL respectively demonstrated favorable diagnostic performance.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 5","pages":"200-207"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585974","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}
Yinlong Li, Xin Zhou, Zhendong Song, Taoqian Zhao, Jian Rong, Jiahui Chen, Chunyu Zhao, Qilong Hu, Xiaoyan Li, Chongjiao Li, Zhenkun Sun, Yabiao Gao, Jimmy S Patel, Ahmad Chaudhary, Hongjie Yuan, Steven H Liang
{"title":"Radiosynthesis and evaluation of a carbon-11 labeled PET ligand for imaging of O-GlcNAcase.","authors":"Yinlong Li, Xin Zhou, Zhendong Song, Taoqian Zhao, Jian Rong, Jiahui Chen, Chunyu Zhao, Qilong Hu, Xiaoyan Li, Chongjiao Li, Zhenkun Sun, Yabiao Gao, Jimmy S Patel, Ahmad Chaudhary, Hongjie Yuan, Steven H Liang","doi":"10.62347/IVXM3055","DOIUrl":"10.62347/IVXM3055","url":null,"abstract":"<p><p>O-GlcNAcase (OGA) is a key enzyme involved in regulating the dynamic cycling of O-GlcNAc modifications on intracellular proteins. OGA has emerged as a promising therapeutic target for neurodegenerative diseases, including Alzheimer's disease. In this report, we present the radiosynthesis and preclinical assessment of a novel carbon-11 labeled positron emission tomography (PET) radioligand [<sup>11</sup>C]1 (codenamed OGA-2504) targeting OGA. The aminopyrimidine-based compound 1 and its corresponding desmethyl precursor were synthesized efficiently with good chemical yields. Radiosynthesis of [<sup>11</sup>C]1 was accomplished <i>via</i> <sup>11</sup>C-methylation, yielding an 8% decay-corrected radiochemical yield with high purity (>98%) and high molar activity (92.5 GBq/µmol). [<sup>11</sup>C]1 exhibited moderate lipophilicity (LogD = 2.11) and excellent <i>in vivo</i> stability in serum. However, preliminary PET imaging revealed low brain uptake and slow clearance of [<sup>11</sup>C]1 in mice, suggesting a need for further structural optimization to enhance brain penetration.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 5","pages":"183-192"},"PeriodicalIF":1.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585880","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}