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

Acknowledgements

CollaboratorsCollaborators• Andrew K. Godwin, Ph.D Andrew K. Godwin, Ph.D • Harvey Hensley, Ph.DHarvey Hensley, Ph.D• Denise Connolly, Ph.DDenise Connolly, Ph.D

Support Support • National Cancer InstituteNational Cancer Institute• GIST Cancer Research FundGIST Cancer Research Fund (Tania Stutman)(Tania Stutman)• NIH institutional trainingNIH institutional training grant (LR)grant (LR)• MerckMerck

FCCC FacilitiesFCCC Facilities• Laboratory Animal FacilityLaboratory Animal Facility• Small Animal Imaging FacilitySmall Animal Imaging Facility

von Mehren Groupvon 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.