SYNTHESIS OF A BIFUNCTIONAL CHELATING AGENT, -AMINOCYCLOHEXYL-1,2-DIAMINO-N,N,N',N'-TETRAACETIC ACID, AND GENERAL-METHOD OF LINKER INTRODUCTION

Indium-111 (In-111) is a radioelement whose radiophysical caracteristi cs are perfectly suitable for diagnostic applications, but are neverth eless limited by a high liver uptake. Undesirable river uptake can be reduced either by using bifunctional chelating agents (BCA) to form st able chelates in vivo or by introducing linkers between the ligand and the antibody that can serve as a target for spectic hepatic enzymes. Various studies have shown that In-111 chelate stability can be improv ed by the use of polyaminocarboxylic BCA and especially with 4-isocyan atocyclohexane-1 ,2-diaminotetraacetic acid (4-ICE). The purpose of ou r study was to synthesize aminocyclohexane-1,2-diamino-N,N,N',N'-tetra acetic acid, an analog of 4-ICE, associated with different bis-N-hydro xysuccinimide ester type bifunctional aliphatic linkers. We propose a simple method for access to perfectly defined BCA with or without pote ntially metabolizable functions.