Prodrug enzymes and their applications in image-guided therapy of cancer: tracking prodrug enzymes to minimize collateral damage

Many cytotoxic therapies are available to kill cancer cells. Unfortunately, these also inflict significant damage on normal cells. Identifying highly effective cancer treatments that have minimal or no side effects continues to be a major challenge. One of the strategies to minimize damage to normal tissue is to deliver an activating enzyme that localizes only in the tumor and converts a nontoxic prodrug to a cytotoxic agent locally in the tumor. Such strategies have been previously tested but with limited success due in large part to the uncertainty in the delivery and distribution of the enzyme. Imaging the delivery of the enzyme to optimize timing of the prodrug administration to achieve image-guided prodrug therapy would be of immense benefit for this strategy. Here, we have reviewed advances in the incorporation of image guidance in the applications of prodrug enzymes in cancer treatment. These advances demonstrate the feasibility of using clinically translatable imaging in these prodrug enzyme strategies.