Purpose Statement: Our goal is to genetically label neural progenitor cells with a dual-reporter PET imaging system, which besides the constitutively induced “beacon” gene would include an inducible neural-specific “sensor” gene. Our hypothesis is that this dual imaging system will facilitate the in vivo monitoring of neural stem cell distribution, migration, differentiation, and persistence. Methods and Materials: PC12 cells and rat mesenchymal stem cells (MSCs) were genetically labeled with a CMV reporter gene driving expression of human thymidine kinase (hTK2) fused to green fluorescent protein (GFP), and imaged with [11C]FEAU or [18F]FEAU. For neural specific tracking, a minimized neural specific enolase (NSE) promoter driving expression of HSV1-sr39tk–RFP (red fluorescent protein) was imaged with [18F]FHBG. Results: PC12 and rat MSCs were successfully imaged with a CMV promoter driving hTK2 using [11C]FEAU and [18F]FEAU. PC12 and MSCs guided to the neural fate using NGF cocktails were simultaneously detected using the neural specific sensor (NSE- HSV1-sr39tk-RFP) and [18F]FHBG. Results were verified in vitro and in vivo using immunohistochemistry, flow analysis, and RT-PCR. Conclusion: We demonstrate the in-vivo molecular detection of progenitor cell conversion into a neural phenotype. This technology will significantly aid in the development and clinical implementation of stem cell-based therapies.