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 of ¹³¹I-MIP-1145 to develop ¹³¹I-iodofluoropicolinamide benzamide (¹³¹I-IFPABZA) and ¹³¹I-iodofluoronicotiamide benzamide (¹³¹I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models. ¹³¹I-IFPABZA (Log P = 2.01) was more lipophilic than ¹³¹I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with ¹³¹I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with ¹³¹I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of ¹³¹I-IFNABZA- and ¹³¹I-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 of ¹³¹I-IFNABZA with the melanin-targeted agents reported in the literature, ¹³¹I-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 using ¹³¹I-IFNABZA as a theranostic agent against melanoma.

Keywords: 131I-iodofluoronicotiamide benzamide (131I-IFNABZA); 131I-iodofluoropicolinamide benzamide (131I-IFPABZA); melanoma; theranostic agent.