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

Jing Zhu, Wen  ,  Kobayashi, Masato  ,  Yamada, Kohei  ,  Nishi, Kodai  ,  Takahashi, Kotaro  ,  Mizutani, Asuka  ,  Nishii, Ryuichi  ,  G. Flores II, Leo  ,  Shikano, Naoto  ,  Kunishima, Munetaka

59pp.16 - 21 , 2018-04 , ELSEVIER
AbstractIntroductionDue 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.MethodsRadioiodine-125-labeled AP (125I–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 125I–AP or 14C(U)-labeled AP (14C–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 125I–AP. The stability of 125I–AP over time was evaluated in mice.ResultsThe labeling efficiency and radiochemical purity of 125I–AP were >80% and 95%, respectively. Accumulation of 125I–AP was higher than that of 14C–AP at 60 min of incubation in vitro. The affinity of 14C–AP for tyrosinase and DNA polymerase was higher than that of 125I–AP, whereas the Vmax of 125I–AP was higher than that of 14C–AP. 125I–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 125I–AP for imaging contrast were the highest at 15 min after injection, whereas the melanoma:blood and melanoma:bone ratios gradually increased over time. 125I–AP remained stable for 60 min after injection in mice.Conclusions125I–AP has affinity for tyrosinase and high image contrast at early time points after injection. Therefore, 123I–AP imaging has great potential for specific, high-contrast detection of malignant melanoma.Advances in Knowledge123I–AP will provide specific, high-contrast imaging for malignant melanoma at early injection times.Implications for patient care123I–AP has good potential for the diagnosis of malignant melanoma compared with 123I–labeled 4-hydroxyphenylcysteamine, which we previously developed.

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