論文

査読有り
2015年6月

Development of radioiodine-labeled 4-hydroxyphenylcysteamine for specific diagnosis of malignant melanoma

NUCLEAR MEDICINE AND BIOLOGY
  • Masato Kobayashi
  • ,
  • Ryuichi Nishii
  • ,
  • Naoto Shikano
  • ,
  • Leo G. Flores
  • ,
  • Asuka Mizutani
  • ,
  • Kazuhiro Ogai
  • ,
  • Jyunko Sugama
  • ,
  • Shigeki Nagamachi
  • ,
  • Keiichi Kawai

42
6
開始ページ
536
終了ページ
540
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.nucmedbio.2015.02.004
出版者・発行元
ELSEVIER SCIENCE INC

Introduction: A specific diagnosis for melanoma is strongly desired because malignant melanoma has poor prognosis. In a previous study, although radioiodine-125-labeled 4-hydroxyphenyl-L-cysteine (I-125-L-PC) was found to have good substrate affinity for tyrosinase enzyme in the melanin metabolic pathway, 1231131 I-L-PC had insufficient substrate affinity for tyrosinase to diagnose melanoma. In this study, we synthesized 4-hydroxyphenylcysteamine (4-PCA) and developed a novel radioiodine-125-labeled 4-hydroxyphenylcysteamine (I-125-PCA) to increase affinity for the melanin biosynthesis pathway.
Methods: 4-PCA was separated with 2-hydroxyphenylcysteamine (2-PCA), which is an isomer of 4-PCA, and was examined using melting point, proton nuclear magnetic resonance, mass spectrometry and elemental analysis. I-125-PCA was prepared using the chloramine-T method under no-carrier added conditions. We performed biodistribution experiments using B16 melanoma-bearing mice using I-125-PCA, I-125-L-pc, I-125-alpha-methyl-L-tyrosine, I-123-m-iodobenzylguanidine and Ga-67-citrate. In vitro assay was performed with B16 melanoma cells, and affinity for tyrosinase, DNA polymerase and amino acid transport was evaluated using phenylthiourea, thymidine, ouabine and L-tyrosine inhibitor. In addition, partition coefficients of I-125-PCA were evaluated.
Results: In the synthesis of 4-PCA, analysis values did not differ between calculated and reported values, and 4-PCA was separated from 2-PCA at high purity. In biodistribution experiments, I-125-PCA was accumulated and retained in B16 melanoma cells when compared with 125I-L-PC. I-125-PCA showed the highest values at 60 min after radiotracer injection in melanoma-to-muscle ratios, melanoma-to-blood ratios and melanoma-to-skin ratios. Accumulation of I-125-PCA was significantly inhibited by phenylthiourea and thymidine. Partition coefficients of I-125-PCA were lower than those of N-isopropyl-p-[I-123]iodoamphetamine and were not significantly different from 125I-L-PC.
Conclusions: I-125-PCA is a better substrate for tyrosinase and DNA polymerase and has higher uptake and longer retention in B16 melanoma cells when compared with 125I-L-PC. Therefore, I-123/131-PCA has good potential for diagnosis for malignant melanoma.
Advance in Knowledge: I-125-PCA will be a specific diagnosis tool for malignant melanoma.
Implications for Patient Care: I-123/131-PCA has good potential for the diagnosis of malignant melanoma when compared with other SPECT tracers, as well as anti-melanoma chemotherapeutic drugs. (C) 2015 Elsevier Inc. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.nucmedbio.2015.02.004
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25744361
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000354662500004&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.nucmedbio.2015.02.004
  • ISSN : 0969-8051
  • eISSN : 1872-9614
  • PubMed ID : 25744361
  • Web of Science ID : WOS:000354662500004

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