Perfusion-Independent Tissue Hypoxia in Cardiac Hypertrophy in Mice Measured by 64Cu-CTS PET Imaging
Background: Hypoxia is central to many cardiac pathologies, but clinically its presence can only be inferred by indirect biomarkers including hypoperfusion and energetic compromise. Imaging hypoxia directly could offer new opportunities for the diagnosis and sub-stratification of cardiovascular diseases. Objectives: To determine whether [64Cu]CuCTS Positron Emission Tomography (PET) can identify hypoxia in a murine model of cardiac hypertrophy. Methods: Male C57BL/6 mice underwent abdominal aortic constriction (AAC) to induce cardiac hypertrophy, quantified by echocardiography over 4 weeks. Hypoxia and perfusion were quantified in vivo using [64Cu]CuCTS and [64Cu]CuGTSM PET, respectively, and radiotracer biodistribution was quantified post-mortem. Cardiac radiotracer retention was correlated with contractile function (measured by echocardiography), cardiac hypertrophy (measured by histology), HIF-1a; stabilization and NMR-based metabolomics. The effect of anesthesia on [64Cu]CuCTS upta