Pub Date : 2025-10-25eCollection Date: 2025-01-01DOI: 10.62347/MRZS8767
Steven H Liang
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.
{"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}
Purpose: To refine the optimal PRIMARY score thresholds across different PSA ranges, enhancing diagnostic accuracy for clinically significant prostate cancer (csPCa).
Methods: 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.
Results: 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.
Conclusion: Across different PSA ranges, the PRIMARY score based on 68Ga-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.
{"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}
Pub Date : 2025-10-25eCollection Date: 2025-01-01DOI: 10.62347/IVXM3055
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
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 [11C]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 [11C]1 was accomplished via11C-methylation, yielding an 8% decay-corrected radiochemical yield with high purity (>98%) and high molar activity (92.5 GBq/µmol). [11C]1 exhibited moderate lipophilicity (LogD = 2.11) and excellent in vivo stability in serum. However, preliminary PET imaging revealed low brain uptake and slow clearance of [11C]1 in mice, suggesting a need for further structural optimization to enhance brain penetration.
{"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}
Pub Date : 2025-08-15eCollection Date: 2025-01-01DOI: 10.62347/XDLP4069
Kenneth J Nichols, Adam Kesner, Kuldeep K Bhargava, Paige Bennett, Christopher J Palestro
Glomerular filtration rates (GFR's) are used to guide patient management. GFR's are based on radioactivity measurements of blood samples sampled at different times. We compared GFR computations from blood collected at 6 times to those collected at 2 timepoints. Thirty-seven GFR studies were performed on 25 patients. After intravenous administration of I-125 sodium iothalamate, 6 plasma samples were obtained at 5 min, 10 min, 15 min, 3 hr, 3.5 hr and 4 hr after injection, then counted in a well counter. Two different GFR calculation tools were applied to each set of 6 plasma counts (Methods 1 and 2), and a 2-sample algorithm (Method 3) computed GFR using only 3 hr and 4 hr data. Linear correlation between Method 1 and 2 GFR's was stronger than for Method 3 versus Methods 1 and 2 (r = 1.00 versus r = .91, P < .0001). Bland-Altman limits of agreement were larger (P < .0001) for Method 3 versus Methods 1 and 2 (-39.5 to +22.0 ml/min/1.73 m2) than for Method 1 versus 2 (-7.6 to +4.5 ml/min/1.73 m2). Method 3 overestimated lower GFR's and underestimated higher GFR's. Methods 1 and 2 agreed exactly in identifying 3 cases of GFR < 74 ml/min/1.73 m2 (κ = 1.00), while Method 3 detected only 1 of the three (κ = .48). To avoid underdiagnosing low GFR's, larger GFR sample sizes are preferable to smaller sample sizes.
{"title":"Effect of truncating blood sampling in measuring glomerular filtration rate.","authors":"Kenneth J Nichols, Adam Kesner, Kuldeep K Bhargava, Paige Bennett, Christopher J Palestro","doi":"10.62347/XDLP4069","DOIUrl":"10.62347/XDLP4069","url":null,"abstract":"<p><p>Glomerular filtration rates (GFR's) are used to guide patient management. GFR's are based on radioactivity measurements of blood samples sampled at different times. We compared GFR computations from blood collected at 6 times to those collected at 2 timepoints. Thirty-seven GFR studies were performed on 25 patients. After intravenous administration of I-125 sodium iothalamate, 6 plasma samples were obtained at 5 min, 10 min, 15 min, 3 hr, 3.5 hr and 4 hr after injection, then counted in a well counter. Two different GFR calculation tools were applied to each set of 6 plasma counts (Methods 1 and 2), and a 2-sample algorithm (Method 3) computed GFR using only 3 hr and 4 hr data. Linear correlation between Method 1 and 2 GFR's was stronger than for Method 3 versus Methods 1 and 2 (r = 1.00 versus r = .91, P < .0001). Bland-Altman limits of agreement were larger (P < .0001) for Method 3 versus Methods 1 and 2 (-39.5 to +22.0 ml/min/1.73 m<sup>2</sup>) than for Method 1 versus 2 (-7.6 to +4.5 ml/min/1.73 m<sup>2</sup>). Method 3 overestimated lower GFR's and underestimated higher GFR's. Methods 1 and 2 agreed exactly in identifying 3 cases of GFR < 74 ml/min/1.73 m<sup>2</sup> (κ = 1.00), while Method 3 detected only 1 of the three (κ = .48). To avoid underdiagnosing low GFR's, larger GFR sample sizes are preferable to smaller sample sizes.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 4","pages":"140-145"},"PeriodicalIF":1.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111809","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}
Pub Date : 2025-08-15eCollection Date: 2025-01-01DOI: 10.62347/OAHP6281
Tilman Speicher, Moritz B Bastian, Arne Blickle, Armin Atzinger, Florian Rosar, Caroline Burgard, Samer Ezziddin
The increasing use of artificial intelligence (AI) chatbots for patient education raises questions about their accuracy, readability, and conciseness in delivering medical information. This study evaluates the performance of ChatGPT 4o and DeepSeek V3 in answering common patient inquiries about Peptide Receptor Radionuclide Therapy (PRRT). Twelve frequently asked patient questions regarding PRRT were submitted to both chatbots. The responses were assessed by nine professionals using a blinded survey, scoring accuracy, conciseness, and readability on a five-point scale. Statistical analyses included the Mann-Whitney U test for nonparametric data and the Chi-square test for medically incorrect responses. A total of 324 individual assessments were conducted. No significant differences were found in accuracy between ChatGPT 4o (mean 4.43) and DeepSeek V3 (mean 4.56; P = 0.0909) or in readability between ChatGPT 4o (mean 4.38) and DeepSeek V3 (mean 4.25; P = 0.1236). However, ChatGPT 4o provided significantly more concise responses (mean 4.55) compared to DeepSeek V3 (mean 4.24; P = 0.0013). Medically incorrect information defined as accuracy ≤ 3 was present in 7-8% of chatbot responses, with no significant difference between the two models (P = 0.8005). Both AI chatbots demonstrated strong performance in providing medical information on PRRT, with ChatGPT 4o excelling in conciseness. However, the presence of medical inaccuracies highlights the need for physician oversight when using AI chatbots for patient education. Future research should explore methods to enhance AI reliability and personalization in clinical communication.
{"title":"Advancing patient education in PRRT through large language models: challenges and potential.","authors":"Tilman Speicher, Moritz B Bastian, Arne Blickle, Armin Atzinger, Florian Rosar, Caroline Burgard, Samer Ezziddin","doi":"10.62347/OAHP6281","DOIUrl":"10.62347/OAHP6281","url":null,"abstract":"<p><p>The increasing use of artificial intelligence (AI) chatbots for patient education raises questions about their accuracy, readability, and conciseness in delivering medical information. This study evaluates the performance of ChatGPT 4o and DeepSeek V3 in answering common patient inquiries about Peptide Receptor Radionuclide Therapy (PRRT). Twelve frequently asked patient questions regarding PRRT were submitted to both chatbots. The responses were assessed by nine professionals using a blinded survey, scoring accuracy, conciseness, and readability on a five-point scale. Statistical analyses included the Mann-Whitney U test for nonparametric data and the Chi-square test for medically incorrect responses. A total of 324 individual assessments were conducted. No significant differences were found in accuracy between ChatGPT 4o (mean 4.43) and DeepSeek V3 (mean 4.56; <i>P</i> = 0.0909) or in readability between ChatGPT 4o (mean 4.38) and DeepSeek V3 (mean 4.25; <i>P</i> = 0.1236). However, ChatGPT 4o provided significantly more concise responses (mean 4.55) compared to DeepSeek V3 (mean 4.24; <b><i>P</i> = 0.0013</b>). Medically incorrect information defined as accuracy ≤ 3 was present in 7-8% of chatbot responses, with no significant difference between the two models (<i>P</i> = 0.8005). Both AI chatbots demonstrated strong performance in providing medical information on PRRT, with ChatGPT 4o excelling in conciseness. However, the presence of medical inaccuracies highlights the need for physician oversight when using AI chatbots for patient education. Future research should explore methods to enhance AI reliability and personalization in clinical communication.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 4","pages":"146-152"},"PeriodicalIF":1.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111815","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}
Pub Date : 2025-08-15eCollection Date: 2025-01-01DOI: 10.62347/IXKG9158
Shiv Patil, Nirmal Patel, Eric Teichner, William Lee, Ehsan Ranjbar, Alexander Gerlach, Robert Subtirelu, Lancelot Herpin, Thomas Werner, Poul Flemming Høilund-Carlsen, Abass Alavi
Osteoporosis is a highly prevalent skeletal disease involving a pathophysiology of altered bone turnover. Positron emission tomography (PET)/computed tomography (CT) imaging with 18F-sodium fluoride (NaF) can visualize metabolic alterations in bone that precede clinical manifestations or structural alterations and thus may serve a role in the early detection and monitoring of osteoporosis. We present two non-oncological case reports demonstrating different metabolic changes in early and advanced disease stages as assessed by 18F-NaF PET/CT that cannot be appreciated by conventional structural imaging alone, supporting a potential clinical application of 18F-NaF PET/CT for early detection and monitoring of osteoporosis in the lumbar spine.
{"title":"<sup>18</sup>F-NaF PET/CT for early detection of osteoporosis in the lumbar spine: two case reports.","authors":"Shiv Patil, Nirmal Patel, Eric Teichner, William Lee, Ehsan Ranjbar, Alexander Gerlach, Robert Subtirelu, Lancelot Herpin, Thomas Werner, Poul Flemming Høilund-Carlsen, Abass Alavi","doi":"10.62347/IXKG9158","DOIUrl":"10.62347/IXKG9158","url":null,"abstract":"<p><p>Osteoporosis is a highly prevalent skeletal disease involving a pathophysiology of altered bone turnover. Positron emission tomography (PET)/computed tomography (CT) imaging with <sup>18</sup>F-sodium fluoride (NaF) can visualize metabolic alterations in bone that precede clinical manifestations or structural alterations and thus may serve a role in the early detection and monitoring of osteoporosis. We present two non-oncological case reports demonstrating different metabolic changes in early and advanced disease stages as assessed by <sup>18</sup>F-NaF PET/CT that cannot be appreciated by conventional structural imaging alone, supporting a potential clinical application of <sup>18</sup>F-NaF PET/CT for early detection and monitoring of osteoporosis in the lumbar spine.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 4","pages":"153-157"},"PeriodicalIF":1.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111795","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}
Pub Date : 2025-08-15eCollection Date: 2025-01-01DOI: 10.62347/KJLM2547
Taoqian Zhao, Steven H Liang
The U.S. Food and Drug Administration (FDA) has proposed a regulatory shift in the early-phase development of positron emission tomography (PET) radiopharmaceuticals, specifically regarding the requirement for animal-based dosimetry in first-in-human (FIH) studies. This editorial discusses the implications of the FDA's recent Advisory Committee briefing, which supports the omission of preclinical dosimetry under defined conditions for radiopharmaceuticals labeled with 18F, 11C, 68Ga, 64Cu, 82Rb, and 13N. The proposed policy reflects a shift toward a more streamlined, evidence-based approach to FIH studies while maintaining stringent standards for patient safety.
{"title":"Streamlining first-in-human PET radiopharmaceutical development: FDA's evolving stance on preclinical dosimetry.","authors":"Taoqian Zhao, Steven H Liang","doi":"10.62347/KJLM2547","DOIUrl":"10.62347/KJLM2547","url":null,"abstract":"<p><p>The U.S. Food and Drug Administration (FDA) has proposed a regulatory shift in the early-phase development of positron emission tomography (PET) radiopharmaceuticals, specifically regarding the requirement for animal-based dosimetry in first-in-human (FIH) studies. This editorial discusses the implications of the FDA's recent Advisory Committee briefing, which supports the omission of preclinical dosimetry under defined conditions for radiopharmaceuticals labeled with <sup>18</sup>F, <sup>11</sup>C, <sup>68</sup>Ga, <sup>64</sup>Cu, <sup>82</sup>Rb, and <sup>13</sup>N. The proposed policy reflects a shift toward a more streamlined, evidence-based approach to FIH studies while maintaining stringent standards for patient safety.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 4","pages":"171-172"},"PeriodicalIF":1.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111741","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}
Pub Date : 2025-08-15eCollection Date: 2025-01-01DOI: 10.62347/ERGQ2963
Taoqian Zhao, Steven H Liang
This symposium provided an extensive overview of emerging positron emission tomography (PET) tracers and targets for Alzheimer's disease (AD) and related dementias (ADRD), highlighting novel approaches for imaging neuroinflammation, neurotransmitter systems, mitochondrial dysfunction, and proteinopathies. Key developments included the harmonization of PET data across cohorts, new tau and alpha-synuclein tracers, and critical advancements in understanding neurodegenerative disease heterogeneity through integrated imaging, genetic, and pathological studies.
{"title":"Novel tracers and emerging targets for positron emission tomography in Alzheimer's disease and related dementias.","authors":"Taoqian Zhao, Steven H Liang","doi":"10.62347/ERGQ2963","DOIUrl":"10.62347/ERGQ2963","url":null,"abstract":"<p><p>This symposium provided an extensive overview of emerging positron emission tomography (PET) tracers and targets for Alzheimer's disease (AD) and related dementias (ADRD), highlighting novel approaches for imaging neuroinflammation, neurotransmitter systems, mitochondrial dysfunction, and proteinopathies. Key developments included the harmonization of PET data across cohorts, new tau and alpha-synuclein tracers, and critical advancements in understanding neurodegenerative disease heterogeneity through integrated imaging, genetic, and pathological studies.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 4","pages":"167-170"},"PeriodicalIF":1.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111759","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}
Pub Date : 2025-08-15eCollection Date: 2025-01-01DOI: 10.62347/IRKD4863
Xiaodan Shi, Zhangxin Wu, Yifeng Yuan, Ying Wang, Shuo Yang, Rong Li
Radiolabeled folate derivatives have been extensively investigated for positron emission tomography (PET) imaging of ovarian cancer due to the frequent overexpression of folate receptor α (FRα). However, clinical translation has been hindered, at least in part, by suboptimal tumor uptake of FRα-targeted radiotracers. In this study, we developed and characterized a 68Ga-labeled heterodimeric radiotracer, 68Ga-folate-KR, designed to concurrently target FRα and human epidermal growth factor receptor 2 (HER2), another receptor commonly overexpressed in ovarian cancer. Transcriptomics analysis confirmed the co-upregulation of FOLR1 and HER2 in ovarian cancer tissues relative to normal ovarian tissue, supporting the rationale for dual-receptor targeting. In vitro binding assays demonstrated specific binding of 68Ga-folate-KR to both receptors. PET imaging and biodistribution studies in SKOV3 tumor-bearing mice revealed significantly enhanced tumor uptake and improved tumor-to-nontumor contrast compared to the monomeric radiotracers 68Ga-folate and 68Ga-KR. Competitive blocking experiments further confirmed the in vivo dual-receptor targeting capability of 68Ga-folate-KR. Collectively, our results highlight that 68Ga-folate-KR enables more sensitive PET detection of ovarian cancer xenografts. With further optimization, dual-receptor-targeted radiotracers hold promise for clinical translation in both lesion detection and therapy response monitoring in ovarian cancer.
{"title":"Dual-receptor PET imaging of ovarian cancer using a <sup>68</sup>Ga-labeled heterodimer targeting folate receptor and HER2.","authors":"Xiaodan Shi, Zhangxin Wu, Yifeng Yuan, Ying Wang, Shuo Yang, Rong Li","doi":"10.62347/IRKD4863","DOIUrl":"10.62347/IRKD4863","url":null,"abstract":"<p><p>Radiolabeled folate derivatives have been extensively investigated for positron emission tomography (PET) imaging of ovarian cancer due to the frequent overexpression of folate receptor α (FRα). However, clinical translation has been hindered, at least in part, by suboptimal tumor uptake of FRα-targeted radiotracers. In this study, we developed and characterized a <sup>68</sup>Ga-labeled heterodimeric radiotracer, <sup>68</sup>Ga-folate-KR, designed to concurrently target FRα and human epidermal growth factor receptor 2 (HER2), another receptor commonly overexpressed in ovarian cancer. Transcriptomics analysis confirmed the co-upregulation of <i>FOLR1</i> and <i>HER2</i> in ovarian cancer tissues relative to normal ovarian tissue, supporting the rationale for dual-receptor targeting. In vitro binding assays demonstrated specific binding of <sup>68</sup>Ga-folate-KR to both receptors. PET imaging and biodistribution studies in SKOV3 tumor-bearing mice revealed significantly enhanced tumor uptake and improved tumor-to-nontumor contrast compared to the monomeric radiotracers <sup>68</sup>Ga-folate and <sup>68</sup>Ga-KR. Competitive blocking experiments further confirmed the in vivo dual-receptor targeting capability of <sup>68</sup>Ga-folate-KR. Collectively, our results highlight that <sup>68</sup>Ga-folate-KR enables more sensitive PET detection of ovarian cancer xenografts. With further optimization, dual-receptor-targeted radiotracers hold promise for clinical translation in both lesion detection and therapy response monitoring in ovarian cancer.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 4","pages":"130-139"},"PeriodicalIF":1.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111773","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}
Pub Date : 2025-08-15eCollection Date: 2025-01-01DOI: 10.62347/SPOE8395
Qi-Huang Zheng, Min Wang, Barbara E Glick-Wilson, Chase A Arkins, Eric R Klueppelberg, Scott E Snyder, Michael L Schulte
O-(2-[18F]Fluoroethyl)- L -tyrosine ([18F]FET) is a promising amino acid PET tracer for assessment of malignant brain tumors. Herein, we report optimized production of [18F]FET for clinical use on two commercial radiochemistry systems: Sofie ELIXYS and GE FASTlab 2. While the Sofie ELIXYS procedure requires high performance liquid chromatography (HPLC) purification, the GE FASTlab 2 method uses solid-phase extraction (SPE) purification. In both cases, [18F]FET met release specifications for clinical investigation laid out in the United States Pharmacopeia (USP) and/or European Pharmacopeia (Ph. Eur.). The radiochemical yield of [18F]FET was 35-55% and 30-55% decay corrected to start of synthesis (SOS) for Sofie ELIXYS and GE FASTlab 2, respectively. The overall synthesis time was 75-85 and 70-80 min from SOS for Sofie ELIXYS and GE FASTlab 2, respectively. The radiochemical purity was > 99%, and the molar activity (Am) was 340-464 GBq/µmol at end of synthesis (EOS).
{"title":"Optimization and comparison of [<sup>18</sup>F]FET synthesis on two distinct automated radiochemistry systems.","authors":"Qi-Huang Zheng, Min Wang, Barbara E Glick-Wilson, Chase A Arkins, Eric R Klueppelberg, Scott E Snyder, Michael L Schulte","doi":"10.62347/SPOE8395","DOIUrl":"10.62347/SPOE8395","url":null,"abstract":"<p><p><i>O</i>-(2-[<sup>18</sup>F]Fluoroethyl)- <i><sub>L</sub></i> -tyrosine ([<sup>18</sup>F]FET) is a promising amino acid PET tracer for assessment of malignant brain tumors. Herein, we report optimized production of [<sup>18</sup>F]FET for clinical use on two commercial radiochemistry systems: Sofie ELIXYS and GE FASTlab 2. While the Sofie ELIXYS procedure requires high performance liquid chromatography (HPLC) purification, the GE FASTlab 2 method uses solid-phase extraction (SPE) purification. In both cases, [<sup>18</sup>F]FET met release specifications for clinical investigation laid out in the United States Pharmacopeia (USP) and/or European Pharmacopeia (Ph. Eur.). The radiochemical yield of [<sup>18</sup>F]FET was 35-55% and 30-55% decay corrected to start of synthesis (SOS) for Sofie ELIXYS and GE FASTlab 2, respectively. The overall synthesis time was 75-85 and 70-80 min from SOS for Sofie ELIXYS and GE FASTlab 2, respectively. The radiochemical purity was > 99%, and the molar activity (A<sub>m</sub>) was 340-464 GBq/µmol at end of synthesis (EOS).</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"15 4","pages":"158-166"},"PeriodicalIF":1.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111818","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}