Project/Area Number |
17390336
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Radiation science
|
Research Institution | Ibaraki Prefectural University of Health Science |
Principal Investigator |
SHIKANO Naoto Ibaraki Prefectural University of Health Science, Department of Radiological Sciences, Assistant Professor (80295435)
|
Co-Investigator(Kenkyū-buntansha) |
SHIKAWA Nobuyoshi Ibaraki Prefectural University of Health Sciences, Department of Radiological Sciences, Professor (10026932)
KAWAI Keiichi Kanazawa University, Faculty of Medicine, Professor (30204663)
|
Project Period (FY) |
2005 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥8,940,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
|
Keywords | radiopharamaceutical / artificial amino acid / L-type amino acid transporter / 4F2hc / neutral amino acid / functional imaging / system L / isoform selectivity / 放射性医薬品 / 人工アミノ酸 / アミノ酸輸送 / 機能診断薬 / 画像診断薬 / L系 / アイソフォーム選択性 |
Research Abstract |
Human L-type amino acid transporter 1 (hLAT1), a component of system L, is expressed in a wide variety of organs. Its highest expression levels are in the brain, placenta, testis, bone marrow and fetal liver, followed by peripheral leukocytes, lymph nodes and the thymus. In a previous study, LAT1 was found to act as a system L transporter at the blood-brain barrier and tumor tissue. On the other hand, hLAT2, an isoform of hLATi, involves in the trans-cellular transport of neutral amino acids in epithelia blood-tissue barriers. Development of isoform-specific amino acid transporter agent is helpful about clarification of amino acid metabolic disease. We examined system-selectivity of 3-[^ (125) I]iodo-α-methyl-L-tyrosine (^<125>IMT), 4-[^<125>I]iodo-L-meta-tyrosine (4-[^<125>I]-mTyr) and 3-[^<125>I]iodo-L-tyrosine (3-[^<125>I]-Tyr) transport in Chinese hamster ovary cell K1 (CHO-K1) and those isoform-selectivity of the two human L-type amino acid transporters, hLAT1 and hLAT2 with human 4F2hc co-expressed Xenopus laevis oocytes. CHO-Klcell line studies have revealed that 4-[^<125>I]-mTyr exhibited the greatest system L specificity (93.46±0.13%) of all the amino acids tested, and therefore shows promise as a system-L-selective amino acid transport marker. [^<125>I]IMT, 4-[^<125>I]-mTyr and 3- [^<125>I] -Tyr transport was hLAT1-selective. Animal studies with these compounds are anticipated in further studies.
|