PT  - JOURNAL ARTICLE
AU  - Shikano, Naoto
AU  - Kawai, Keiichi
AU  - Flores, Leo Garcia
AU  - Nishii, Ryuichi
AU  - Kubota, Nobuo
AU  - Ishikawa, Nobuyoshi
AU  - Kubodera, Akiko
TI  - An Artificial Amino Acid, 4-Iodo-<span class="sc">l</span>-<em>meta</em>-Tyrosine: Biodistribution and Excretion via Kidney
DP  - 2003 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 625--631
VI  - 44
IP  - 4
4099  - http://jnm.snmjournals.org/content/44/4/625.short
4100  - http://jnm.snmjournals.org/content/44/4/625.full
SO  - J Nucl Med2003 Apr 01; 44
AB  - 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 radiolabeled 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.