Evaluating new therapies in GIST using in vivo molecular imaging Lori Rink, Ph.D Fox Chase Cancer Center

Molecular imaging and personalized medicine Genome and expression analyses will identify molecules and pathways activated in individual cancers Opportunity for individually tailored therapy Plethora of available agents – need for prioritization Biological therapies frequently less toxic – tumors may not shrink Resistance – via target mutation or compensatory pathway activation Need for imaging modalities to detect biological/functional response –CT –MRI –PET Can molecular imaging be used for rapid assessment of drug efficacy? –Individualization of therapy, dose and/or schedule –Combination of targeted therapeutic agents

Reduced light absorption by abundant molecules (e.g., hemoglobin) Reduced autofluorescence Probes - maximum light penetration and high sensitivity Quantitative Detect biological activities/molecular targets Limited tissue penetration In vivo near infrared fluorescent (NIRF) molecular imaging

Fluorescent molecular tomography:FMT FMT2500 – VisEn Medical -3D quantitative measurements of probe activation and/or retention Provides non-invasive, whole body, deep tissue imaging in small animal models to generate 3D, information-rich results. -Functional imaging of biological and physiological changes Biological targets and pathways can be monitored and quantified in real time - giving a deeper understanding of the biology underlying disease mechanisms and therapeutic response.

Evaluating novel therapeutics using in vivo molecular imaging

AcknowledgementsCollaborators Andrew K. Godwin, Ph.D Andrew K. Godwin, Ph.D Harvey Hensley, Ph.D Harvey Hensley, Ph.D Denise Connolly, Ph.D Denise Connolly, Ph.D Support National Cancer Institute National Cancer Institute GIST Cancer Research Fund GIST Cancer Research Fund (Tania Stutman) (Tania Stutman) NIH institutional training NIH institutional training grant (LR) grant (LR) Merck Merck FCCC Facilities Laboratory Animal Facility Laboratory Animal Facility Small Animal Imaging Facility Small Animal Imaging Facility von Mehren Group Margaret von Mehren, M.DMargaret von Mehren, M.D Martin Belinsky, Ph.D.Martin Belinsky, Ph.D. Alexis Cordero, B.S.Alexis Cordero, B.S.