Renal accumulation and excretion of radioiodinated 3-iodo-alpha-methyl-L-tyrosine.
OBJECTIVE
We investigated mechanisms of renal accumulation of radioiodinated 3-iodo-alpha-methyl-L-tyrosine (IMT), which has been used clinically for tumor imaging and as an amino acid transport marker in studies of brain and pancreas function.


METHODS
In this study, we used 125I- or 123I-labeled IMT ([125I]IMT or [123I]IMT) as the transport marker. Partition coefficients of [125I]IMT were determined for hypothetic urine at pH ranging from 5 to 8. The examination of uptake and inhibition of [125I]IMT was performed using normal human renal proximal tubule epithelial cells (RPTEC), which are characteristic of the proximal convoluted tubule. The plasma protein binding ratio of [125I]IMT was determined using rats. In the in vivo experiments using mice, we examined biodistribution and excretion inhibition, and performed whole body autoradiography. Also, renal SPECT using [123I]IMT was performed using a normal canine.


RESULTS
Very low lipophilicity of [125I]IMT in hypothetic urine suggests that a carrier-mediated pathway contributes to its marked kidney accumulation. [125I]IMT uptake into RPTEC was significantly inhibited by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) in a sodium-dependent manner, suggesting reabsorption mainly via system B0 in apical membrane of proximal tubule. Plasma protein binding ratio of IMT was 45.4 +/- 5.6%. At 6 hr after administration of IMT to mice, excretion via urinary tract was 77.51% of injected dose, and excretion into feces was 0.25%. Furosemide, ethacrynic acid and probenecid inhibited tubular secretion of [125I]IMT in mice. We obtained very clear autoradiographs of mouse renal cortex and a canine renal SPECT image (S2-like region).


CONCLUSIONS
We believe that [123I]IM-T is useful for kidney imaging. In future studies, we plan to examine the use of [123I]IMT in diagnosis of disease.
Shikano
Naoto
N
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Inashiki-gun, Japan. sikano@ipu.ac.jp
Kawai
Keiichi
K
Nakajima
Syuichi
S
Nishii
Ryuichi
R
Flores
Leo Garcia
LG
Kubodera
Akiko
A
Kubota
Nobuo
N
Ishikawa
Nobuyoshi
N
Saji
Hideo
H
D000818:Animals; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008781:Methyltyrosines / Q000378:metabolism / Q000493:pharmacokinetics*; D051379:Mice; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D014018:Tissue Distribution
D008781:Methyltyrosines; D019275:Radiopharmaceuticals; C030855:3-iodo-alpha-methyltyrosine