Comprehensive MRI, MRS and Molecular Analyses: Pten-based Prostate Cancer Models
Recent advances in prostate Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) have enhanced the noninvasive diagnosis of clinical PCa have improved its monitoring following treatment.
Despite the advances in human prostate cancer (PCa) imaging, the ability to evaluate the interrelationship between specific genetic lesions and the induction and progression of tumorigenesis as well as treatment remains extremely difficult in human subjects. Modeling of human PCa using engineered mice that contain activated signaling pathways or other lesions found in clinical samples is a critical tool for investigations into the molecular mechanisms of initiation and progression of this disease. In mouse models, however, tumor development can be slow and the time of initiation is variable. Animal sacrifice is necessary for disease evaluation due to the location of the prostate, complicating longitudinal studies. Hypothesis: We propose that MRI will help identify early morphometric changes and will allow for the in vivo identification of initiated prostate disease. Additionally we propose that in vivo MRS will allow for the assessment of cancer progression through the identification of biochemical markers of advanced PCa. Co-registration of these data will further enable preselection of diseased prostate tissue for molecular pathological analyses performed ex vivo. These experiments will be performed on our biologically accurate mouse models of PCa, the MRI and MRS data combined with the follow-up mechanistic and histopathology data provide a unique mechanism to help facilitate the identification of bio- and molecular- markers of clinical PCa.