<i>N</i>-(2-(Dimethylamino)Ethyl)-4-¹⁸F-Fluorobenzamide: A Novel Molecular Probe for High-Contrast PET Imaging of Malignant Melanoma.

Abstract

Malignant melanoma is an aggressive and serious form of skin cancer, with prognosis and treatment outcome depending heavily on the clinical stage of the disease at the time of diagnosis. Here, we synthesized a novel ¹⁸F-labeled benzamide derivative to target melanoma and then evaluated its biologic characteristics in small-animal models. <b>Methods:</b><i>N</i>-(2-(dimethylamino)ethyl)-4-¹⁸F-fluorobenzamide (¹⁸F-DMFB) was synthesized by reaction of <i>N</i>-succinimidyl 4-¹⁸F-fluorobenzoate with <i>N,N</i>-dimethylethylenediamine. The binding affinity of ¹⁸F-DMFB was measured in B16F10 (mouse melanoma) cells with or without l-tyrosine. Small-animal PET imaging with ¹⁸F-DMFB was performed on B16F10 xenograft and metastasis mouse models. <b>Results:</b> The overall non-decay-corrected radiochemical yield of ¹⁸F-DMFB was approximately 10%-15%. Uptake of ¹⁸F-DMFB was melanin-specific, as cellular uptake in B16F10 increased more than 18-fold in the presence of l-tyrosine. Biodistribution studies revealed that ¹⁸F-DMFB accumulated, and was retained, in B16F10 xenografts for 120 min (10, 30, 60, and 120 min: 9.24, 10.80, 13.0, and 10.59 percentage injected dose/g, respectively) after radiotracer injection. Liver uptake of ¹⁸F-DMFB decreased from 10 to 120 min and showed fast clearance (10, 30, 60, and 120 min: 11.19, 5.7, 2.47, and 0.4 percentage injected dose/g). Furthermore, ¹⁸F-DMFB allowed visualization of metastatic lesions immediately after injection and was retained in lesions for over 60 min, with a high tumor-to-background ratio. <b>Conclusion:</b>¹⁸F-DMFB demonstrated a high melanin-targeting ability and tumor-specific tumor uptake in both primary and metastatic lesions in animal models bearing malignant melanoma. ¹⁸F-DMFB may be a potential PET imaging agent for melanoma.