Abstract
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Objectives Malignant melanoma is a serious type of skin cancer. Melanin was a very attractive target of malignant melanoma for diagnosis and treatment. In this study we report 123/131I-Iochlonicotiamide, a benzamide analogue specifically targeted to melanin, as a novel SPECT probe in a melanoma-bearing mouse model.
Methods 123/131I-Iochlonicotiamide was prepared from a self-synthesized precursor via oxidative radioiodination with acceptable radiochemical yield (~30%, decay corrected) and high radiochemical purity (>98%) after HPLC purification. Biological characterization including cellular uptake, biodistribution, and microSPECT/CT imaging were performed in C57BL6 female mice bearing B16F0 melanoma.
Results 123/131I-Iochlonicotiamide displayed good in vitro stability (> 90% at 24 h in mouse serum) and medium hydrophilicity (logP=0.78). In vitro cellular uptake (in %ID/106 cells) studies showed rapid accumulation in B16F0 melanoma cells (8.37±0.06 at 15 min, 10.22±0.40 at 2 h), while the uptake in amelanonic A375 melanoma cells was much lower (1.96±0.02 at 15 min and 1.99±0.06 at 2 h incubation, respectively). In biodistribution study, significant uptake in tumor and eyeball was noticed. Obvious radioactivity accumulation in stomach at 1 h postinjection may indicate partial deiodination of 123/131I-Iochlonicotiamide in vivo. Static microSPECT/CT imaging of mice bearing B16F0 melanoma clearly delineated tumor lesion at 4 h and 24 h postinjection, consistent with that observed in biodistribution studies.
Conclusions A novel radioiodinated benzamide analogue, 123/131I-Iochlonicotiamide, was successfully synthesized and evaluated in cultured melanonic and amelanonic melanoma cells and tumor-bearing mice. The results of biological characterization indicated that 123/131I-Iochlonicotiamide is a promising SPECT probe for malignant melanoma