HSV-1 viral oncolysis and molecular imaging with PET

Viral oncolysis, the destruction of cancer cells by replicating viruses, is a new modality of cancer therapy. This strategy involves use of viruses that are either genetically engineered to replicate preferentially in neoplastic cells, or use of viruses that display innate tropism for neoplastic cells. These viruses may also be modified to deliver transgenes to destroy cancer cells. While numerous viruses may be used for this form of cancer therapy, HSV-1 is an attractive vector for viral oncolysis due to several characteristics including its high infectivity, ease of genetic engineering, large transgene capacity, and the availability of an effective medical treatment for Herpes simplex virus infections. The HSV-1 viral genome has been manipulated to generate replication conditional viruses which target cancer cells. Although these viruses are programmed to replicate preferentially in cancer cells, there is some unintended replication in normal cells. Currently, biopsy is the gold standard for monitoring the therapeutic effects of viral oncolysis. However, a non-invasive test capable of serial monitoring of therapy during the treatment period is required for both preclinical and clinical studies. Positron emission tomography (PET) using HSV thymidine kinase as the PET reporter gene offers the desired qualities of a non-invasive test which can be easily repeated to determine the location and magnitude of viral replication and tumor lysis. We review viral oncolysis, focusing on HSV-1 viral oncolysis and therapeutic monitoring by PET.