Evaluation of radioiodinated fluoronicotinamide/ fluoropicolinamide-benzamide derivatives as theranostic agents for melanoma

Abstract

Malignant melanoma is the most harmful type of skin cancer and its incidence has increased in this past decade. Early diagnosis and treatment are urgently desired. In this study, we conjugated picolinamide/nicotinamide with the pharmacophore of131 I-MIP-1145 to develop131 I-iodofluoropicolinamide benzamide (131 I-IFPABZA) and131 I-iodofluoronicotiamide benzamide (131 I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models.131 I-IFPABZA (Log P = 2.01) was more lipophilic than131 I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with131 I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with131 I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of131 I-IFNABZA-and131 I-IFPABZA-injected mice only showed marginal tumor uptake in A375 amelanotic melanoma-bearing mice throughout the experiment period, indicating the high binding affinity of these two radiotracers to melanin. Comparing the radiation-absorbed dose of131 I-IFNABZA with the melanin-targeted agents reported in the literature,131 I-IFNABZA exerts lower doses to normal tissues on the basis of similar tumor dose. Based on the in vitro and in vivo studies, we clearly demonstrated the potential of using131 I-IFNABZA as a theranostic agent against melanoma.