Optical imaging for Translational Cancer Research

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DESCRIPTION (provided by applicant): The importance of imaging small animals in basic and translational biomedical research, with such modalities as PET, SPECT, CT, optical, ultrasound, and MRI, cannot be over- emphasized. The ability to image small animals without sacrificing them, allows investigators to a) validate novel probes for diagnosis, b) conduct in vivo pharmacokinetic studies, c) evaluate investigational bio-molecules for prevention and therapy, and d) determine the effectiveness of therapy. Small animal imaging reduces the number of animals necessary for studies and controls cost, while providing scientifically valid and statistically significant data. At Thomas Jefferson University (TJU), there are more than 300 basic and physician scientists engaged in biomedical research in oncology, neurology, and cardiology. Four years ago, TJU established a small animal imaging facility that is directed by the PI in the Department of Radiology. The facility includes a CT, a PET/SPECT, and a PET scanner. This facility has thus far been used by 33 investigators and produced more than 30 articles in peer-reviewed journals. In longitudinal studies, animals receive radiation doses at variable levels and frequency. Concerns are raised regarding the unknown consequences of this radiation, particularly in such studies as effectiveness of therapeutic intervention, angiogenesis inhibition, and imaging apoptosis. At the same time, investigators realize that in optical imaging any fluorescent dye that compromises visualization of a lesion due to its depth in the body can be radiolabeled for PET or SPECT imaging. The roles of scintigraphic and optical imaging are complimentary, and we will use the two modalities synergistically. For example, a successful PNA construct developed in our laboratory that enables PET imaging of kRAS oncogene mRNA in xenografts when labeled with Cu-64 has been labeled with a near infrared (NIR) dye, NIR664, for successful optical imaging of human colorectal cancer xenografts in mice. Similarly, a Cu-64 labeled VPAC oncogene receptor specific peptide developed in our laboratory for human breast cancer imaging also lends itself for NRI imaging of malignant lesions in human breast. Other investigators at TJU demonstrate similar needs. Available to us with the existing PET/SPECT/CT imaging facility are the institutional support, ancillary devices, animal models, and institutionally approved protocols. The addition of optical imaging facility will strongly enhance our research capability at TJU. PUBLIC HEALTH RELEVANCE: Translational biomedical research in which laboratory discoveries are translated into clinical diagnosis and treatment relies heavily on molecular research. The proposed optical imaging facility will enable our biomedical investigators to perform non-invasive imagining in a synergistic and complementary fashion accelerating the bench to bedside transition.