Preparation and characterization of a novel Al¹⁸F-NOTA-BZA conjugate for melanin-targeted imaging of malignant melanoma

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• 作者：Chih-Chao Chang^a ; Chih-Hsien Chang^a ; ^b ; Yi-Hsuan Lo^a ; Ming-Hsien Lin^c ; Chih-Chieh Shen^d ; Ren-Shyan Liu^a ; ^e ; ^f ; Hsin-Ell Wang^a ; ^{hewang@ym.edu.tw" class="auth_mail" title="E-mail the corresponding author} ; Chuan-Lin Chen^a ; ^{clchen2@ym.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：NOTA ; Melanoma ; Benzamide ; Al&ndash ; F complex ; Positron emission tomography
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：26
• 期：16
• 页码：4133-4139
• 全文大小：1308 K

文摘

Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. Previous studies have demonstrated the specific binding ability of benzamide moiety to melanin. In this study, we developed a novel ¹⁸F-labeled NOTA–benzamide conjugate, Al¹⁸F–NOTA–BZA, which can be synthesized in 30 min with a radiochemical yield of 20–35% and a radiochemical purity of >95%. Al¹⁸F–NOTA–BZA is highly hydrophilic (log P = −1.96) and shows good in vitro stability. Intravenous administration of Al¹⁸F–NOTA–BZA in two melanoma-bearing mouse models revealed highly specific uptake in B16F0 melanotic melanoma (6.67 ± 0.91 and 1.50 ± 0.26% ID/g at 15 and 120 min p.i., respectively), but not in A375 amelanotic melanoma (0.87 ± 0.21 and 0.24 ± 0.09% ID/g at 15 and 120 min p.i., respectively). The clearance from most normal tissues was fast. A microPET scan of Al¹⁸F–NOTA–BZA-injected mice also displayed high-contrast tumor images as compared with normal organs. Owing to the favorable in vivo distribution of Al¹⁸F–NOTA–BZA after intravenous administration, the estimated absorption dose was low in all normal organs and tissues. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and the low projected human dosimetry supported that Al¹⁸F–NOTA–BZA is a very promising melanin-specific PET probe for melanin-positive melanoma.