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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
出版社(者): THE SOCIETY OF NUCLEAR MEDICINE INC
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
LLC-PK1
SPECT
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)

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