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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, \u003e70% of 4-125I-mTyr was excreted via the urine, whereas \u003c5% 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 \u003e98.1% of the total present in kidney and \u003e96.3% 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. 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An artificial amino acid, 4-iodo-L-meta-tyrosine: Biodistribution and excretion via kidney
http://hdl.handle.net/2297/2789
http://hdl.handle.net/2297/27893499554e-1cbf-412c-8272-14d18a5e233f
名前 / ファイル | ライセンス | アクション |
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ME-PR-SHIKANO-N-625.pdf (302.4 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-03 | |||||
タイトル | ||||||
タイトル | An artificial amino acid, 4-iodo-L-meta-tyrosine: Biodistribution and excretion via kidney | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Shikano, Naoto
× Shikano, Naoto× Kawai, Keiichi× Garcia Flores II, Leo× Nishii, Ryuichi× Kubota, Nobuo× Ishikawa, Nobuyoshi× Kubodera, Akiko |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学大学院医学系研究科 | |||||
書誌情報 |
Journal of Nuclear Medicine 巻 44, 号 4, p. 625-631, 発行日 2003-04-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0161-5505 | |||||
NCID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA00703684 | |||||
出版者 | ||||||
出版者 | THE SOCIETY OF NUCLEAR MEDICINE INC | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |