Development of radioiodine labeled acetaminophen for specific, high-contrast imaging of malignant melanoma.

Introduction: Due to its poor prognosis, specific imaging for early detection of malignant melanoma is strongly desired. Although radioiodine labeled 4-hydroxyphenylcysteamine, which we previously developed, has good affinity for tyrosinase, an enzyme in the melanin metabolic pathway, image contrast of the melanoma:organ ratios is not sufficiently high for detection of primary melanoma and metastases at early injection times. In this study, we developed radioiodine labeled acetaminophen (I-AP) for specific, high-contrast imaging of malignant melanoma.

Methods: Radioiodine-125-labeled AP (I-AP) was prepared using the chloramine-T method under no carrier-added conditions. Accumulation of radioactivity and the mechanism were evaluated in vitro using B16 melanoma cells incubated with I-AP or C(U)-labeled AP (C-AP) with and without l-tyrosine as a substrate of tyrosinase, phenylthiourea as an inhibitor of tyrosinase, and thymidine as an inhibitor of DNA polymerase. The biological distribution of radioactivity in B16 melanoma-bearing mice was evaluated to determine the accumulation of I-AP. The stability of I-AP over time was evaluated in mice.

Results: The labeling efficiency and radiochemical purity of I-AP were >80% and 95%, respectively. Accumulation of I-AP was higher than that of C-AP at 60 min of incubation in vitro. The affinity of C-AP for tyrosinase and DNA polymerase was higher than that of I-AP, whereas the V of I-AP was higher than that of C-AP. I-AP showed the highest accumulation in the gall bladder, and clearance from the blood and kidney was rapid. Melanoma:muscle and melanoma:normal skin ratios of I-AP for imaging contrast were the highest at 15 min after injection, whereas the melanoma:blood and melanoma:bone ratios gradually increased over time. I-AP remained stable for 60 min after injection in mice.

Conclusions: I-AP has affinity for tyrosinase and high image contrast at early time points after injection. Therefore, I-AP imaging has great potential for specific, high-contrast detection of malignant melanoma. ADVANCES IN KNOWLEDGE: I-AP will provide specific, high-contrast imaging for malignant melanoma at early injection times. IMPLICATIONS FOR PATIENT CARE: I-AP has good potential for the diagnosis of malignant melanoma compared with I-labeled 4-hydroxyphenylcysteamine, which we previously developed.