Document Detail


An artificial amino acid, 4-iodo-L-meta-tyrosine: biodistribution and excretion via kidney.
MedLine Citation:
PMID:  12679409     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-(125)I-iodo-L-meta-tyrosine (4-(125)I-mTyr). Results obtained for L-(14)C-Tyr and 3-(125)I-iodo-alpha-methyl-L-tyrosine ((125)I-IMT) were used for comparison. METHODS: In vivo biodistribution studies of 4-(125)I-mTyr were performed in male ddY mice. Urinary excretion of 4-(125)I-mTyr and (125)I-IMT with administration of probenecid was studied. Local distribution of 4-(125)I-mTyr and (125)I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-(125)I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-(125)I-mTyr were compared with those of (125)I-IMT and the parent L-(14)C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK(1) in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na(+)-free medium, and at 4 degrees C. RESULTS: 4-(125)I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of (125)I-IMT. Blood clearance of 4-(125)I-mTyr was faster than that of (125)I-IMT. Three hours after administration, >70% of 4-(125)I-mTyr was excreted via the urine, whereas <5% was found in the feces. Renal autoradiography revealed moderate accumulation of 4-(125)I-mTyr and high accumulation of (125)I-IMT in the renal cortex. Probenecid further reduced accumulation of 4-(125)I-mTyr and (125)I-IMT in the kidney as well as urinary excretion. At 30 min after tracer injection, intact free 4-(125)I-mTyr accounted for >98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-(125)I-mTyr into LLC-PK(1) cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4 degrees C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-(14)C-Tyr and (125)I-IMT showed similar results; however, uptake of (125)I-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-(125)I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radiolabeled L-Tyr analogs. 4-(125)I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-(125)I-mTyr demonstrates different pharmacologic features than those of (125)I-IMT, particularly in renal handling. 4-(125)I-mTyr may potentially be applied as a new amino acid transport marker.
Authors:
Naoto Shikano; Keiichi Kawai; Leo Garcia Flores; Ryuichi Nishii; Nobuo Kubota; Nobuyoshi Ishikawa; Akiko Kubodera
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Validation Studies    
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  44     ISSN:  0161-5505     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-07     Completed Date:  2003-05-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  625-31     Citation Subset:  IM    
Affiliation:
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394, Japan. sikano@ipu.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / chemical synthesis,  pharmacokinetics,  urine
Animals
Autoradiography
Carbon Radioisotopes / pharmacokinetics,  pharmacology,  urine
Cell Line
Epithelial Cells / drug effects,  metabolism*
Feasibility Studies
Female
Injections, Intravenous
Iodine Radioisotopes / pharmacokinetics,  urine
Kidney / cytology,  drug effects,  metabolism*
Methyltyrosines / pharmacokinetics,  urine
Mice
Mice, Inbred Strains
Organ Specificity
Probenecid / pharmacology
Sensitivity and Specificity
Swine
Tissue Distribution
Tyrosine / pharmacokinetics,  urine
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Carbon Radioisotopes; 0/Iodine Radioisotopes; 0/Methyltyrosines; 14684-02-7/3-iodo-alpha-methyltyrosine; 55520-40-6/Tyrosine; 57-66-9/Probenecid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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