Positron emission tomography (PET) reporter genes (PRGs), when coupled with positron-emitting PET reporter probes (PRPs), are useful for tracking specific cell populations in cell-based therapies, in transgenic animal models, and in xenograft tumor progression experiments. The activities of incorporated PRGs in targeted cells can be monitored noninvasively by PET imaging in preclinical in vivo studies and clinical applications following systemic administration of the appropriate PRG. Here we describe a method that minimizes both design and variability of vector delivery vehicles for alternative PRGs and biological variability of the in vivo target when comparing the efficacy, sensitivity, and specificity of alternative PRG/PRP combinations for in vivo PRG imaging. The principles described for comparing alternative PRG/PRP reporter gene systems can be applied to comparisons of alternative fluorescence, bioluminescence, single-photon emission computerized tomography (SPECT), and magnetic resonance imaging (MRI) reporter genes.
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