Synthesis and evaluation of macrocyclic amino acid derivatives for tumor imaging by gallium-68 positron emission tomography

Ga-68 PET imaging in clinical oncology represents a notable development because the availability of Ga-68 is not dependent on a cyclotron. Furthermore, labeled amino acid derivatives have been proven to be useful for the imaging many tumor types. In the present study, we synthesized beta-aminoalanine, gamma-aminohomoalanine, and lysine conjugates of macrocyclic bifunctional chelating agents, such as, NOTA (1a-c) and DOTA (2a-c). The compounds produced were found to be potential useful as Ga-68-PET imaging agents. In particular, they showed high tumor uptakes in vitro and in vivo, and had high labeling yields and excellent stabilities. The co-ordination chemistry of NOTA-monoamide compound 1a was studied by multinuclear NMR. In vitro studies showed that the synthesized compounds were taken up by cancer cells more than controls (Ga-68-NOTA and Ga-68-DOTA). Furthermore, in vivo studies showed that they have high tumor to muscle and tumor to blood ratios, and small-animal PET imaging revealed high tumor uptakes as compared with other organs, and high bladder activities, indicating rapid renal excretion. These results might motivate the use of Ga-68 amino acid PET for tumor diagnosis. (C) 2010 Elsevier Ltd. All rights reserved.