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

Abstract

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 (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.

RESULTS:

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.

CONCLUSIONS:

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. ADVANCES IN KNOWLEDGE: 123I-AP will provide specific, high-contrast imaging for malignant melanoma at early injection times. IMPLICATIONS FOR PATIENT CARE: 123I-AP has good potential for the diagnosis of malignant melanoma compared with 123I-labeled 4-hydroxyphenylcysteamine, which we previously developed.

• Authors: Wen Jing Zhu, Masato Kobayashi, Kohei Yamada, Kodai Nishi, Kotaro Takahashi, Asuka Mizutani, Ryuichi Nishii, Leo G Flores 2nd, Naoto Shikano, Munetaka Kunishima, Keiichi Kawai
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 59 Pg. 16-21 (04 2018) ISSN: 1872-9614 [Electronic] United States
• PMID: 29413752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Iodine Radioisotopes
• Acetaminophen
• Iodine-125

Topics

• Acetaminophen (chemistry, pharmacokinetics)
• Animals
• Iodine Radioisotopes
• Isotope Labeling
• Male
• Melanoma, Experimental (diagnostic imaging, metabolism)
• Mice
• Molecular Imaging (methods)
• Tissue Distribution