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タイトル: An artificial amino acid, 4-iodo-L-meta-tyrosine: Biodistribution and excretion via kidney
著者: Shikano, Naoto
Kawai, Keiichi link image link image
Garcia Flores II, Leo
Nishii, Ryuichi
Kubota, Nobuo
Ishikawa, Nobuyoshi
Kubodera, Akiko
川井, 惠一
発行日: 2003年 4月
引用: Journal of Nuclear Medicine 44 (4), pp. 625-631
雑誌名: Journal of Nuclear Medicine
ISSN: 0161-5505
巻: 44
号: 4
開始ページ: 625
終了ページ: 631
キーワード: 4-iodo-L-meta-tyrosine
Amino acid transport
Artificial amino acid
抄録: We evaluated the use of radiolabeled 4-iodo-L-meta-tyrosine as an amino acid transport marker. The pharmacologic features of this compound, particularly the biodistribution and excretion, were examined by conducting in vivo and in vitro studies using 4-125I-iodo-L-meta-tyrosine (4- 125I-mTyr). Results obtained for L-14C-Tyr and 3- 125I-iodo-α-methyl-L-tyrosine (125I-IMT) were used for comparison. Methods: In vivo biodistribution studies of 4- 125I-mTyr were performed in male ddY mice. Urinary excretion of 4-125I-mTyr and 125I-IMT with administration of probenecid was studied. Local distribution of 4-125I-mTyr and 125I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-125I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-125I-mTyr were compared with those of 125I-IMT and the parent L-14C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK1 in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na +-free medium, and at 4°C. Results: 4-125I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of 125I-IMT. Blood clearance of 4-125I-mTyr was faster than that of 125I-IMT. Three hours after administration, >70% of 4-125I-mTyr was excreted via the urine, whereas <5% was found in the feces. Renal autoradiography revealed moderate accumulation of 4-125I-mTyr and high accumulation of 125I-IMT in the renal cortex. Probenecid further reduced accumulation of 4-125I-mTyr and 125I-IMT in the kidney as well as urinary excretion. At 30 min after tracer injection, intact free 4-125I-mTyr accounted for >98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-125I-mTyr into LLC-PK1 cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4°C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-14C-Tyr and 125I-IMT showed similar results; however, uptake of 125I-IMT was enhanced by 0.1 mmol/L 2,4-dinitrophenol (165.1%), an inhibitor of generation of energy-rich phosphates. Conclusion: The artificial amino acid 4-125I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radioiabeled L-Tyr analogs. 4-125I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-125I-mTyr demonstrates different pharmacologic features than those of 125I-IMT, particularly in renal handling. 4-125I-mTyr may potentially be applied as a new amino acid transport marker.
URI: http://hdl.handle.net/2297/2789
関連URI: http://jnm.snmjournals.org/misc/terms.shtml
資料種別: Journal Article
版表示: publisher
出現コレクション:1. 査読済論文(医学・保健)

このアイテムを引用あるいはリンクする場合は次の識別子を使用してください。 http://hdl.handle.net/2297/2789



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