Hongyan Feng, Ning Tu, Ke Wang, Xiaowei Ma, Zhentao Zhang, Zhongchun Liu, Zhen Cheng, Lihong Bu
{"title":"猕猴黑质的神经黑素靶向 18 F-P3BZA PET/MR 成像。","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":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"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\":3,\"journal\":{\"name\":\"ACS Applied Electronic Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"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\":\"ACS Applied Electronic Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13550-024-01136-z\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ELECTRICAL & ELECTRONIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13550-024-01136-z","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","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.
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