神经黑色素主要位于黑质（SN）致密部的多巴胺能神经元中，可以通过磁共振成像（MRI）检测到。它是一种有前景的神经系统疾病成像生物标志物。我们之前开发了一种黑色素特异性探针 N-(2-(二乙氨基)-乙基)-18F-5-氟吡啶酰胺 (18F-P3BZA)，最初是为黑色素瘤成像而开发的。 18F-P3BZA 在体外和体内表现出与黑色素的高水平结合，具有高保留性和良好的药代动力学。在本研究中，我们进一步研究了 18F-P3BZA 是否可用于定量检测健康恒河猴 SN 中的神经黑色素。 18F-P3BZA 表现出所需的疏水性，估计 log Know 5.08 和 log D7.4 1.68。 18F-P3BZA 很容易穿过血脑屏障，脑转运系数 (Kin) 为 40±±8 µL g-1s-1。 18F-P3BZA 在神经黑色素 PC12 细胞、富含黑色素的黑色素瘤细胞和黑色素瘤异种移植物中特异性积累。 60 分钟时，18F-P3BZA 与 B16F10 细胞的结合远高于与 SKOV3 细胞的结合（分别为 6.17±0.53%IA 和 0.24±0.05%IA）。在生物分布研究中，18F-P3BZA在B16F10肿瘤中的积累（6.31±0.99%IA/g）高于SKOV3肿瘤中的积累（0.25±0.09%IA/g）。同时，B16F10肿瘤中18F-P3BZA的摄取可以被过量的冷19F-P3BZA阻断（0.81±0.02%IA/g，88%抑制，p<0.05）。 PET/MRI 18F-P3BZA 在健康猕猴注射后 30-60 分钟提供了富含神经黑色素的 SN 的清晰可视化。注射后 30 分钟和 60 分钟，SN 与小脑的比率分别增加了 2.7 和 2.4 倍。在体外放射自显影研究中， 18F-P3BZA 表现出与 SN 的高水平结合，而与周围中脑组织几乎没有结合。 18F-P3BZA PET/MRI 清晰地成像 SN 中的神经黑色素，并可能有助于相关神经系统疾病的早期诊断神经黑色素表达异常。© 2024。作者。

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.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.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.© 2024. The Author(s).