Evaluation of 111In-labeled macrocyclic chelator-amino acid derivatives for cancer imaging

Purpose: We evaluated new In-111-labeled amino acid derivatives, in which the amino acids are conjugated with1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) or 1,4,7,10-tetraazacyclododectine-1,4,7-triacetic acid (DO3A). Methods: DOTA-aminoalanine (DOTA-A), DOTA-aminohomoalanine (DOTA-H), DOTA-lysine (DOTA-L), DO2A-alanine (DO2A-A), DO3A-alanine (DO3A-A) and DO3A-homoalanine (DO3A-H) were labeled with I In. In vitro cell uptake assays were performed usingHep3B (a human hepatoma cell line), CT26 (a mouse colon cancer cell line) and U87MG (a human glioma cell line). In vitro cell uptake inhibition assays were performed using U87MG and In-111-DO3A-H. U87MG bearing xenografted mice were subject to biodistribution, SPECT imaging, autoradiography, and immunohistochemistry studies. Results: Of the amino acid derivatives and cell lines examined, U87MG and In-111-DO3A-14 showed highest uptake in vitro. This uptake was blocked by 2-aminobicyclo-[2,2,1] heptane-2-carboxylic acid (BCH) and by tryptophan. In-111-DO3A-HSPECT imaging of U87MG bearing xenografted mice visualized tumors (mean tumor-to-muscle ratio 3.16 +/- 0.74). Autoradiography and immunohistochemistry revealed that In-111-DO3A-H uptake matched L-type amino acid transporter 1 expression. Conclusion: Tumor uptake was successfully imaged using In-111-DO3A-H in U87MG bearing xenografted mice. In-111-DO3A-H appears to be useful for imaging tumors expressing L-type amino acid transporter. (C) 2012 Elsevier Inc. All rights reserved.