The in vivo sensitivity limits and quantification performance of Cerenkov luminescence imaging have been studied using a tissue-like mouse phantom and 90Y. For a small, 9 mm deep target in the phantom, with no background activity present, the Cerenkov luminescence 90Y detection limit determined from contrast-to-noise ratios is 10 nCi for a 2 min exposure with a sensitive CCD camera and no filters. For quantitative performance, the values extracted from regions of interest on the images are linear within 5% of a straight line fit versus target activity for target activity of 70 nCi and above. The small branching ratio to decay with positron emission for 90Y also permits low-statistics PET imaging of the radionuclide. For PET imaging of the same phantom, with a small animal LSO detector-based scanner, the 90Y detection limit is approximately 3 orders of magnitude higher at 10 µCi.