Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers

The imaging of hypoxia is important for therapeutic decision making in various diseases. 68Ga is an important radionuclide for positron emission tomography (PET), and its usage is increasing, due to the development of the 68Ge/68Ga-generator. In the present study, the authors synthesized two nitroimidazole derivatives by conjugating nitroimidazole and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via an amide bond (4) and a thiourea bond (5). Both derivatives were labeled with 68Ga with high labeling efficiency and were stable after labeling. The low partition coefficients (log P) of 68Ga-4 (−4.6) and 68Ga-5 (−4.5) demonstrated the hydrophilic natures of the derivatives, and both showed higher uptake in cancer cell lines cultured under hypoxic condition than under normoxic condition. However, 68Ga-5 showed higher liver uptake than 68Ga-4 in a biodistribution study due to higher lipophilicity. In an animal PET study, 68Ga-4 showed higher standard uptake values (SUV) in tumors than 68Ga-5 in mice xenografted with CT-26 mouse colon cancer cells.

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