Combination of pet imaging with viral vectors for identification of cancer metastases

There are three main ways for dissemination of solid tumors: direct invasion, lymphatic spread and hematogenic spread. The presence of metastases is the most significant factor in predicting prognosis and therefore evidence of metastases will influence decision-making regarding treatment. Conventional imaging techniques are limited in the evaluation and localization of metastases due to their restricted ability to identify subcentimeter neoplastic disease. Hence, there is a need for an effective noninvasive modality that can accurately identify occult metastases in cancer patients. One such method is the combination of positron emission tomography (PET) with vectors designed for delivery of reporter genes into target cells. Vectors expressing the herpes simplex virus-1 thymidine kinase (HSV1-tk) reporter system have recently been shown to allow localization of micrometastases in animal models of cancer using non invasive imaging. Combination of HSV1-tk and PET imaging is based on the virtues of vectors which can carry and selectively express the HSV1-tk reporter gene in a variety of cancer cells but not in normal tissue. A radioactive tracer which is applied systemically is phosphorylated by the HSV1-tk enzyme, and as a consequence, the tracer accumulates in proportion to the level of HSV1-tk expression which can be imaged by PET. s paper we review the recent developments in molecular imaging of micrometastases using replication-competent viral or nonviral vectors carrying the HSV1-tk gene using PET imaging. These diagnostic paradigms introduce an advantageous new concept in noninvasive molecular imaging with the potential benefits for improving patient care by providing guidance for therapy to patients with risk for metastases.