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Optical Bioluminescence and Positron Emission Tomography Imaging of a Novel Fusion Reporter Gene in Tumor Xenografts of Living Mice

Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology [P. R., A. M. W., S. S. G.], University of California at Los Angeles–Jonsson Comprehensive Cancer Center [S. S. G.], and Department of Biomathematics [S. S. G.], David Geffen School of Medicine, University of California, Los Angeles, California 90095

Noninvasive imaging of reporter gene expression using various imaging modalitiesis playing an increasingly important role in defining molecular events in the field of cancer biology, cell biology, and gene therapy. In this study, a novel reporter vector was constructed encoding a fusion protein comprised of a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) (tk), a positron emission tomography (PET) reporter gene, and renilla luciferase (rl), a bioluminescence optical reporter gene joined by a 20 amino acid long spacer sequence. We validated the activity of the two enzymes encoded by the fusion protein (tk₂₀rl) in cell culture. Then, tumors stably expressing the tk₂₀rl fusion gene were imaged both by microPET and optically using a cooled charge coupled device camera in xenograft-bearing living mice. Using a single fusion reporter (PET/optical) gene should accelerate the validation of reporter gene approaches developed in cell culture for translation into preclinical and clinical models.

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