An artificial amino acid, 4-iodo-L-meta-tyrosine: Biodistribution and excretion via kidney

金沢大学大学院医学系研究科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 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

Development of an Automated Synthesis Apparatus for [13N]-labeled Compounds Using Anhydrous [13N]Ammonia.

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