Clinical trials using novel molecular imaging cancer biomarkers: Current status and future directions

Abstract

Abstract The ability to assay cancer biologic features is key to advances in the both the basic biomedical science and clinical patient care. Advances in our ability to assay molecular processes including gene expression, protein expression, and molecular and cellular biochemistry have fueled recent advances in our understanding of many diseases and our ability to treat them. Most assays require sampling of cells or tissue to perform the measurements. Thus the cell culture system, animal model, or patient must be perturbed in order to perform the assay. This requirement makes serial assays over time more difficult and leaves open the possibility that the assay itself may change the state of the system being measured. The ability to measure biologic processes without perturbing them would be highly desirable and would offer complementary information to that obtained by most traditional assay methods. The ability to image regional biochemistry and molecular biology, termed molecular imaging [1,2] offers great promise in using molecular imaging as a cancer biomarker. Quantitative capability is an important feature of molecular imaging, for example, the ability to measure regional tumor receptor expression. The quantitative and non-invasive nature of molecular imaging makes it a potentially very powerful tool for cancer drug development and testing and for translational science [3]. This talk will review the use of molecular imaging as a biomarker, particular positron emission tomography (PET). Examples will be shown using PET imaging to (1) provide prognostic information based upon in vivo measures of cancer differentiation and aggressiveness, (2) measure the regional expression of possible therapeutic targets, (3) provide early assessment of response to therapy. Current clinical trials involving PET as a cancer biomarker will be reviewed, including those using PET radiopharmaceuticals beyond 18F-fluoridexoyglucose (FDG) [3, 4]. The spectrum of current trials will be discussed, with an emphasis on current NCI and ACRIN clinical trials of novel imaging probes, and an eye towards matching future trials of targeted cancer therapy with companion molecular imaging trials.