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Neuromelanin-targeted 18F-P3BZA PET/MR imaging of the substantia nigra in rhesus macaques

文献类型：期刊论文

作者Feng, Hongyan1; Tu, Ning1; Wang, Ke1; Ma, Xiaowei2; Zhang, Zhentao3; Liu, Zhongchun4; Cheng, Zhen5; Bu, Lihong1
刊名EJNMMI RESEARCH
出版日期2025-11-24
卷号15期号:1页码:9
关键词F-18-P3BZA Neuromelanin Sequential PET/MR Substantia nigra SWI
ISSN号2191-219X
DOI10.1186/s13550-025-01297-5
英文摘要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)-F-18-5-fluoropicolinamide (F-18-P3BZA), which was initially developed for the imaging of melanoma. F-18-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 F-18-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques. Results F-18-P3BZA exhibited desired hydrophobicity with estimated log K ow 5.08 and log D7.4 1.68. F-18-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 +/- 8 mu L g-1s-1. F-18-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. F-18-P3BZA binding was significantly higher in B16F10 cells vs. amelanotic SKOV3 cells (6.17 +/- 0.53%IA vs. 0.24 +/- 0.05%IA) and in pigmented PC12 cells vs. non-pigmented PC12 cells(7.09 +/- 0.15%IA and 0.29 +/- 0.05%IA).In the biodistribution study, F-18-P3BZA had higher accumulation in B16F10 tumors (6.31 +/- 0.99%IA/g) than in SKOV3 tumors (0.25 +/- 0.09%IA/g). Meanwhile, F-18-P3BZA uptake in B16F10 tumors could be blocked by excess cold F-19-P3BZA (0.81 +/- 0.02%IA/g, 88% inhibition, p < 0.05). PET/MRI F-18-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 vitro autoradiography studies F-18-P3BZA exhibited high levels of binding to the SN of healthy human and almost no binding to the SN of Parkinson's disease patient. Conclusion F-18-P3BZA PET/MRI clearly images neuromelanin in the SN, and may assist in the early diagnosis of neurological diseases associated with abnormal neuromelanin expression.
WOS关键词IN-VITRO ; BRAIN
资助项目the Medical Science Advancement Program of Wuhan University[TFLC 2018001] ; The National Natural Science Foundation of China[81871419] ; The National Natural Science Foundation of China[82101548] ; The National Natural Science Foundation of China[U2267221] ; Key Technologies Research and Development Program of China[2018YFC1314600]
WOS研究方向Radiology, Nuclear Medicine & Medical Imaging
语种英语
WOS记录号WOS:001622337500001
出版者SPRINGER
源URL[http://119.78.100.183/handle/2S10ELR8/322043]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Cheng, Zhen; Bu, Lihong
作者单位1.Wuhan Univ, Nucl Med & PET CT MRI Ctr, Renmin Hosp, 99 Zhangzhidong Rd, Wuhan 430060, Hubei, Peoples R China
2.Cent South Univ, Xiangya Hosp 2, Dept Nucl Med, Changsha, Hunan, Peoples R China
3.Wuhan Univ, Dept Neurol, Renmin Hosp, Wuhan, Hubei, Peoples R China
4.Wuhan Univ, Dept Psychiat, Renmin Hosp, Wuhan, Hubei, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Feng, Hongyan,Tu, Ning,Wang, Ke,et al. Neuromelanin-targeted 18F-P3BZA PET/MR imaging of the substantia nigra in rhesus macaques[J]. EJNMMI RESEARCH,2025,15(1):9.
APA Feng, Hongyan.,Tu, Ning.,Wang, Ke.,Ma, Xiaowei.,Zhang, Zhentao.,...&Bu, Lihong.(2025).Neuromelanin-targeted 18F-P3BZA PET/MR imaging of the substantia nigra in rhesus macaques.EJNMMI RESEARCH,15(1),9.
MLA Feng, Hongyan,et al."Neuromelanin-targeted 18F-P3BZA PET/MR imaging of the substantia nigra in rhesus macaques".EJNMMI RESEARCH 15.1(2025):9.

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来源：上海药物研究所

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