Synthesis and evaluation of a novel radioiodinated phenylacetamide as a SPECT probe for malignant melanoma

Objectives Melanoma is one of the most deadly cancers around the world. Melanin is an attractive target of malignant melanoma for diagnosis and treatment. This study reports N-(2-(diethylamino)ethyl)-2-(4-hydroxy-3-^123/131I-iodophenyl)acetamide (^123/131I-IPA) as a novel SPECT probe for imaging malignant melanoma.

Methods ^123/131I-IPA can be prepared from a self-synthesized precursor via oxidative radioiodination with high radiochemical yield (>70%) and high radiochemical purity (>95%). Biological characterizations including cellular uptake, biodistribution and microSPECT imaging were performed in mice bearing various melanomas.

Results ^123/131I-IPA is hydrophilic (log P = -0.76±0.04) and exhibited good in vitro stability (radiochemical purity >95% after a 24-h incubation) in human serum. ^123/131I-IPA exhibited a high affinity (88.78±0.66 %AD) to synthetic melanin (0.5 mg/10 mL) after 1 h of incubation. A rapid and high uptake of ^123/131I-IPA by B16F0 melanoma cells after 0.25, 1 and 4 h of incubation was observed (10.07±0.45, 15.62±0.72 and 19.22±0.62 %AD/10⁶ cells, respectively), while that by amelanonic A375 cells was much lower (1.62±0.13, 1.30±0.11 and 0.90±0.05 %AD/10⁶ cells, respectively). A remarkable accumulation in melanoma and eyeballs of C57BL6 mice post intravenous injection (p.i.) was noticed. The tumor-to-muscle ratio was 17.5, 26.3 and 62.0 at 1, 4 and 24 h p.i., respectively, consistent with those observed in microSPECT imaging which displayed a high contrast B16F0 melanoma lesion.

Conclusions Our studies demonstrated that ^123/131I-IPA, a novel phenylacetamide derivative, is a melanin-specific agent for imaging malignant melanoma with SPECT.

Research Support This study was supported by grants from National Science Council, Taiwan (NSC 100-2314-B-010-013 and NSC 101-2314-B-010-044-MY3) and Cheng Hsin General Hospital, Taiwan (102F218C08)