| 17998105 |
Nakajima S, Shikano N, Kotani T, Ogura M, Nishii R, Yoshimoto M, Yamaguchi N, Iwamura Y, Kubota N, Ishikawa N, Kawai K: Pharmacokinetics of 3-[125I] iodo-alpha-methyl-L-tyrosine, a tumor imaging agent, after probenecid loading in mice implanted with colon cancer DLD-1 cells. Nucl Med Biol. 2007 Nov;34(8):1003-8. Epub 2007 Sep 4.
INTRODUCTION: In order to improve tumor imaging, changes in the pharmacokinetics of 3-[123I] iodo-alpha-methyl-l-tyrosine ([123I] IMT), an artificial amino acid that exhibits high tumor accumulation, after probenecid (PBC) loading was studied in mice implanted with colon cancer DLD-1 cells using 125I-labeled IMT ([125I] IMT). METHODS: DLD-1-implanted KSN-slc nude male mice received 740 kBq of [125I] IMT via the tail vein at 5 min after 50 mg/kg body weight PBC loading, and autoradiography was performed at 5, 15 and 30 min after injection. Male ddY mice then received 670 kBq of [125I] IMT and 50 mg/kg 2-amino-bicyclo [2,2,1] heptane-2-carboxylic acid (BCH) or p-aminohippurate (PAH) via the tail vein, and kidney autoradiography was performed at 5 min after injection. In vitro inhibition study was then performed based on the accumulation mechanisms of [125I] IMT in DLD-1, using 1 mM l-tyrosine, BCH, alpha-(methylamino)-isobutyric acid, N-benzoyl-beta-alanine, PBC, PAH, 2,4-dinitrophenol and sodium azide. Both Na+-dependent and Na+-independent uptake were investigated. RESULTS: Higher tumor accumulation in PBC-loaded DLD-1-implanted mice was seen when compared to control mice. PAH and BCH, respectively, reduced renal accumulation in the tubule segment-2 (S2)-like and S1-like regions. We confirmed that [125I] IMT transport is predominantly mediated by l-type amino acid transporter-1 in DLD-1 cells. CONCLUSIONS: [125I] IMT uptake is mediated by organic anion and amino acid transporters in the kidney. Organic anion transporter inhibitors may yield better tumor images with good tumor/normal tissue radioactivity ratios if adequate administration plans are developed. |
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