Tumor imaging with (68)Ga-positron emission tomography: synthesis and characterization of macrocycle-amino acid derivatives

Abstract

68Ga positron emission tomography (PET) imaging in clinical oncology is a noted development due to cyclotron independent availability. Labeled amino acid derivatives have been proved useful in imaging many kinds of tumors. We synthesized 3-aminoalanine, 4-aminohomoalanine and lysine derivatives of macrocyclic chelating agents by conjugating amino acids to mono carboxylic group of NOTA and DOTA using either EDC or DCC. Pure compounds were labeled with 68Ga (labeling efficiency N95%, Specific Activity ~ 1.94-9.21 GBq/μmol). The preliminary evaluation was studied in Hep3B and CT-26 cancer cells, which showed high uptake of these derivatives. Highest in vivo tumor uptake was showed by 68Ga-NOTAaminohomoalanine (2.40±0.85% ID/g) at 30 min. PET images in mice bearing CT-26 xenografts showed high tumor uptake for 68Ga-NOTAaminohomoalanine (standard uptake value ratio=12.3±0.05), followed by 68Ga-DOTA-aminoalanine (5.9±0.4). The co-ordination chemistry of NOTA-mono amide compound was studied by multinuclear nuclear magnetic resonance analysis. These studies showed the feasibility of using 68Ga amino acid PET for tumor diagnosis.