Masato Kobayashi MS, Presenter: Nothing to Disclose

Ryuichi Nishii MD, PhD, Abstract Co-Author: Nothing to Disclose

Naoto Shikano PhD, Abstract Co-Author: Nothing to Disclose

Mitsuyoshi Yoshimoto PhD, Abstract Co-Author: Nothing to Disclose

Keiichi Kawai PhD, Abstract Co-Author: Nothing to Disclose

Yasuhisa Fujibayashi PhD, Abstract Co-Author: Nothing to Disclose

Norito Takamura PHD, Abstract Co-Author: Nothing to Disclose

Shigeki Nagamachi MD,PHD, Abstract Co-Author: Nothing to Disclose

Shozo Tamura MD,PhD, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

From the view point of improvement of drug accumulation in target organs, to keep its blood concentration high, which is followed by transient competitive inhibition of renal excretion, may induce its higher uptake to target tissues. Tubular secretion mainly contributes to renal excretion of drugs and many drugs are excreted in urine via organic anion transporters (OAT) on tubular epithelial cell. 3-Iodo-a-methyl-L-tyrosine (I-AMT) is a clinically promising tumor-seeking amino acid agent and we reported it accumulates in the pancreas and the brain by L-type amino acid transporters. Our recent basic experiments also revealed the possibility of the suppression on its renal excretion by OAT inhibition. In present study, we investigated the effects of OAT inhibitors on I-AMT tissue accumulation in in-vivo.

Probenecid, N-benzoyl-b-alanine and cefazolin were used as OAT inhibitors which are clinically available. OAT inhibitors were injected intravenously in mice respectively. Five minutes after injection of them, I-125 AMT was injected intravenously in mice and biodistribution study was conducted. Examination with Tc-99m MAG3 was also performed as a comparison.

Inhibition of renal excretion by probenecid affected biodistribution pattern of I-125 AMT. In mice with probenecid, accumulation of I-125 AMT in kidneys was decreased and that in blood was remarkably increased (1.1-2.4 times) compared with unloaded mice. In addition, brain and pancreas accumulation of I-125 AMT was achieved up to 1.8 times and 3.4 times compared with unloaded mice, respectively. Tc-99m MAG3 also showed the slow clearance in OAT inhibitors loaded mice as compared with unloaded mice. Radioactivity in blood of Tc-99m MAG3 was 3.5 times higher in probenecid loaded mice than in unloaded mice.

As our expected hypothesis, regulation of renal excretion by OAT inhibitors was able to achieve the improvement of I-125 AMT accumulation in brain and pancreas. Furthermore, this regulation technique of renal excretion may control tissue distribution of radiopharmaceuticals in clinical application.

Kobayashi, M, Nishii, R, Shikano, N, Yoshimoto, M, Kawai, K, Fujibayashi, Y, Takamura, N, Nagamachi, S, Tamura, S, et al, , Effect of OAT Inhibition in Renal Excretion of 3-[125I]Iodo-a-methyl-L-tyrosine Scintigraphy to Improve Image Contrast.  Radiological Society of North America 2005 Scientific Assembly and Annual Meeting, November 27 - December 2, 2005 ,Chicago IL. http://archive.rsna.org/2005/4414673.html