Recent advance in molecular pharmacological studies on radioiodinated 3-iodo-α-methyl-L-tyrosine, an L-type amino acid transporter 1-selective tumor imaging agent for SPECT
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概要
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The transport of large neutral amino acids with branched or aromatic side chains is mediated by amino acid transport system L, which is currently being targeted for the development of diagnostic agents for use in the field of tumor nuclear medicine, because system L is conspicuously up-regulated in many tumors and transformed cell lines. Radioiodinated 3-iodo-α-methyl-L-tyrosine (IMT) is a metabolically stable amino acid that exhibits high tumor accumulation and fast renal elimination of intact IMT. It has been reported that the majority of transport of IMT in tumor cells involves the Na^+-independent system L (>70%), and that the Na^+-dependent transport system is responsible for a relatively minor amount of transport (<20%). The Michaelis constant (Km) of IMT has been found to be approximately 10 to 100 μM. Shikano N and colleagues recently examined the isoform-selectivity of IMT transport of the 2 human L-type amino acid transporters (components of system L), LAT1 and LAT2, using Xenopus laevis oocytes co-expressing human LAT1 and human 4F2hc ; IMT transport was LAT1-selective. LAT1 is expressed in many kinds of tumor tissues at higher levels than in normal tissues. Mouse studies indicate that an organic anion transporter also mediates IMT excretion from the kidney. These findings may partly explain the mechanisms underlying the high tumor accumulation and fast renal elimination of IMT. IMT appears to be a promising tool for future research on tumor imaging and amino acid transport imaging with single photon emission computed tomography.
- 茨城県立医療大学の論文
著者
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SHIKANO Naoto
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences
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Shikano Naoto
Department Of Radiological Sciences Ibaraki Prefectural University Of Health Sciences
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