In summary, we have developed a pro-drug strategy for the non-invasive imaging of ALDH activity in animal models of human ovarian cancer. Here, acylals were employed as an in vivo cleavable protecting group for the aromatic aldehyde of a highly-specific ALDH1A1 radiotracer. In cell culture, the aldehyde [ In vivo, the acylal group at trace levels was rapidly cleaved in the blood, the extent of which was substantially reduced through co-injection of the isotopologue [ 19 F]2. PET imaging of [ 18 F]2 in tumour-bearing mice at high and low molar activities revealed tumour-specific uptake, but was unable to distinguish between high and low ALDH-expressing tumours. Future studies will both explore alternative methods to increase the blood half-life of [ 18 F]2 through carrier-added studies using compounds that are substrates for esterases but not ALDH1A1, and fine-tune the protecting group's chemical properties for improved blood stability.