Hongyan Feng, Ning Tu, Ke Wang, Xiaowei Ma, Zhentao Zhang, Zhongchun Liu, Zhen Cheng, Lihong Bu
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In this study we further investigated whether <sup>18</sup>F-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques.</p><p><strong>Results: </strong><sup>18</sup>F-P3BZA exhibited desired hydrophobicity with estimated log Know 5.08 and log D7.4 1.68. <sup>18</sup>F-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 ± 8 µL g-1s-1. <sup>18</sup>F-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. Binding of <sup>18</sup>F-P3BZA to B16F10 cells was much higher than to SKOV3 cells at 60 min (6.17 ± 0.53%IA and 0.24 ± 0.05%IA, respectively). In the biodistribution study, <sup>18</sup>F-P3BZA had higher accumulation in B16F10 tumors (6.31 ± 0.99%IA/g) than in SKOV3 tumors (0.25 ± 0.09%IA/g). Meanwhile, <sup>18</sup>F-P3BZA uptake in B16F10 tumors could be blocked by excess cold <sup>19</sup>F-P3BZA (0.81 ± 0.02%IA/g, 88% inhibition, p < 0.05). PET/MRI <sup>18</sup>F-P3BZA provided clear visualization of neuromelanin-rich SN at 30-60 min after injection in healthy macaques. The SN to cerebella ratios were 2.7 and 2.4 times higher at 30 and 60 min after injection. In in vitro autoradiography studies <sup>18</sup>F-P3BZA exhibited high levels of binding to the SN, and almost no binding to surrounding midbrain tissues.</p><p><strong>Conclusion: </strong><sup>18</sup>F-P3BZA PET/MRI clearly images neuromelanin in the SN, and may assist in the early diagnosis of neurological diseases associated with abnormal neuromelanin expression.</p>","PeriodicalId":11611,"journal":{"name":"EJNMMI Research","volume":"14 1","pages":"79"},"PeriodicalIF":3.1000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372002/pdf/","citationCount":"0","resultStr":"{\"title\":\"Neuromelanin-targeted 18 F-P3BZA PET/MR imaging of the substantia nigra in rhesus macaques.\",\"authors\":\"Hongyan Feng, Ning Tu, Ke Wang, Xiaowei Ma, Zhentao Zhang, Zhongchun Liu, Zhen Cheng, Lihong Bu\",\"doi\":\"10.1186/s13550-024-01136-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Neuromelanin is mostly located in dopaminergic neurons in the substantia nigra (SN) pars compacta, and can be detected by magnetic resonance imaging (MRI). It is a promising imaging-base biomarker for neurological diseases. We previously developed a melanin-specific probe N-(2-(diethylamino)-ethyl)-<sup>18</sup>F-5-fluoropicolinamide (<sup>18</sup>F-P3BZA), which was initially developed for the imaging of melanoma. <sup>18</sup>F-P3BZA exhibited high levels of binding to the melanin in vitro and in vivo with high retention and favorable pharmacokinetics. In this study we further investigated whether <sup>18</sup>F-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques.</p><p><strong>Results: </strong><sup>18</sup>F-P3BZA exhibited desired hydrophobicity with estimated log Know 5.08 and log D7.4 1.68. <sup>18</sup>F-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 ± 8 µL g-1s-1. <sup>18</sup>F-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. Binding of <sup>18</sup>F-P3BZA to B16F10 cells was much higher than to SKOV3 cells at 60 min (6.17 ± 0.53%IA and 0.24 ± 0.05%IA, respectively). In the biodistribution study, <sup>18</sup>F-P3BZA had higher accumulation in B16F10 tumors (6.31 ± 0.99%IA/g) than in SKOV3 tumors (0.25 ± 0.09%IA/g). Meanwhile, <sup>18</sup>F-P3BZA uptake in B16F10 tumors could be blocked by excess cold <sup>19</sup>F-P3BZA (0.81 ± 0.02%IA/g, 88% inhibition, p < 0.05). PET/MRI <sup>18</sup>F-P3BZA provided clear visualization of neuromelanin-rich SN at 30-60 min after injection in healthy macaques. The SN to cerebella ratios were 2.7 and 2.4 times higher at 30 and 60 min after injection. In in vitro autoradiography studies <sup>18</sup>F-P3BZA exhibited high levels of binding to the SN, and almost no binding to surrounding midbrain tissues.</p><p><strong>Conclusion: </strong><sup>18</sup>F-P3BZA PET/MRI clearly images neuromelanin in the SN, and may assist in the early diagnosis of neurological diseases associated with abnormal neuromelanin expression.</p>\",\"PeriodicalId\":11611,\"journal\":{\"name\":\"EJNMMI Research\",\"volume\":\"14 1\",\"pages\":\"79\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372002/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13550-024-01136-z\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJNMMI Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13550-024-01136-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Neuromelanin-targeted 18 F-P3BZA PET/MR imaging of the substantia nigra in rhesus macaques.
Background: Neuromelanin is mostly located in dopaminergic neurons in the substantia nigra (SN) pars compacta, and can be detected by magnetic resonance imaging (MRI). It is a promising imaging-base biomarker for neurological diseases. We previously developed a melanin-specific probe N-(2-(diethylamino)-ethyl)-18F-5-fluoropicolinamide (18F-P3BZA), which was initially developed for the imaging of melanoma. 18F-P3BZA exhibited high levels of binding to the melanin in vitro and in vivo with high retention and favorable pharmacokinetics. In this study we further investigated whether 18F-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques.
Results: 18F-P3BZA exhibited desired hydrophobicity with estimated log Know 5.08 and log D7.4 1.68. 18F-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 ± 8 µL g-1s-1. 18F-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. Binding of 18F-P3BZA to B16F10 cells was much higher than to SKOV3 cells at 60 min (6.17 ± 0.53%IA and 0.24 ± 0.05%IA, respectively). In the biodistribution study, 18F-P3BZA had higher accumulation in B16F10 tumors (6.31 ± 0.99%IA/g) than in SKOV3 tumors (0.25 ± 0.09%IA/g). Meanwhile, 18F-P3BZA uptake in B16F10 tumors could be blocked by excess cold 19F-P3BZA (0.81 ± 0.02%IA/g, 88% inhibition, p < 0.05). PET/MRI 18F-P3BZA provided clear visualization of neuromelanin-rich SN at 30-60 min after injection in healthy macaques. The SN to cerebella ratios were 2.7 and 2.4 times higher at 30 and 60 min after injection. In in vitro autoradiography studies 18F-P3BZA exhibited high levels of binding to the SN, and almost no binding to surrounding midbrain tissues.
Conclusion: 18F-P3BZA PET/MRI clearly images neuromelanin in the SN, and may assist in the early diagnosis of neurological diseases associated with abnormal neuromelanin expression.
EJNMMI ResearchRADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING&nb-
CiteScore
5.90
自引率
3.10%
发文量
72
审稿时长
13 weeks
期刊介绍：
EJNMMI Research publishes new basic, translational and clinical research in the field of nuclear medicine and molecular imaging. Regular features include original research articles, rapid communication of preliminary data on innovative research, interesting case reports, editorials, and letters to the editor. Educational articles on basic sciences, fundamental aspects and controversy related to pre-clinical and clinical research or ethical aspects of research are also welcome. Timely reviews provide updates on current applications, issues in imaging research and translational aspects of nuclear medicine and molecular imaging technologies.
The main emphasis is placed on the development of targeted imaging with radiopharmaceuticals within the broader context of molecular probes to enhance understanding and characterisation of the complex biological processes underlying disease and to develop, test and guide new treatment modalities, including radionuclide therapy.
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