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

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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide