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

• Published in: Nuclear medicine and biology Vol. 59; pp. 16 - 21
• Main Authors: Zhu, Wen Jing, Kobayashi, Masato, Yamada, Kohei, Nishi, Kodai, Takahashi, Kotaro, Mizutani, Asuka, Nishii, Ryuichi, Flores, Leo G., Shikano, Naoto, Kunishima, Munetaka, Kawai, Keiichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2018; Elsevier BV
• Subjects: Accumulation; Acetaminophen; Affinity; Analgesics; Blood; Carbon 14; Chloramine-T; Deoxyribonucleic acid; DNA; DNA polymerase; DNA-directed DNA polymerase; Gallbladder; Image contrast; Incubation; Inhibitors; Injection; Iodine 131; Iodine radioisotopes; Kidneys; Malignant melanoma; Medical imaging; Melanin; Melanoma; Metastases; Mice; Muscles; Phenylthiourea; Radioactivity; Radiochemistry; Radioiodine; Rodents; Skin; SPECT imaging; Stability analysis; Substrate inhibition; Thymidine; Tyrosinase; Tyrosine; Uranium; Radioiodine; SPECT imaging; Acetaminophen; Tyrosinase; Malignant melanoma
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2017.12.008

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. Radioiodine-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. The 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. 125I-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. 123I-AP will provide specific, high-contrast imaging for malignant melanoma at early injection times. 123I-AP has good potential for the diagnosis of malignant melanoma compared with 123I-labeled 4-hydroxyphenylcysteamine, which we previously developed.