expression in cancer and drug effects on these expressions are studied in vivo with genetically engineered light-emitting reporter genes. this also allows the identification of mechanisms for tissue-selective gene targeting in cancer and beyond. combined pet-optical imaging, fluorescence multi-color fluorescence imaging of living hela cells with labelled mitochondria (red), actin (green), and nuclei (bue). each cell is ~10 um and images show optical imaging allows for resolution ≤1 um. principle: dioxaborolane chemistry enables radioactive fluoride (18f) labeling of antibodies or red blood cells, which allows for positron emission tomography (pet) and fluorescence imaging of cancer and hemorrhages, respectively. a human-derived, genetic, positron-emitting and fluorescent (hd-gpf) reporter system uses a human protein, psma and non-immunogenic, and a small molecule that is positron-emitting (boron bound 18f) and fluorescent for dual modality pet and fluorescence imaging of genome modified cells, e.g. cancer, crispr/cas9, or car t-cells, in an entire mouse. the combining of these imaging modalities was predicted by 2008 nobel laureate, roger y. tsien, to compensate for the weaknesses of single imaging techniques. strengths: combines the strengths of pet and optical imaging, fluorescence. pet allows for anatomical imaging for location of labelled cells in entire animals or humans because the radiolabel, 18f, is within the animal or human for nearly unlimited depth of penetration. 18f has a half-life of 110 min and limits the radioactive exposure to the animal or human. optical imaging allows for higher resolution with sub-cellular resolution of ~270 nm, or the diffraction limit of light, to allow for imaging of single cells and localizing cellular location on the cell membrane, endosomes, cytoplasm, or nuclei (see figure of multicolor hela cellls). the technique can label small molecules, antibodies, cells (cancer and red blood cells), cerebrospinal fluid, hemorrhages, prostate cancer removal, and genome edited cells expressing a genetically encoded human protein, psma, for imaging crispr/cas9 edited and car t-cells. weaknesses: combining pet and optical imaging allows for two imaging agents that compensate for the weakness of the others. 18f has a half-life of 110 min and the pet signal is not permanent. fluorescent small molecules allow for permanent signal when stored in the dark and not photobleached. currently, there is not a single instrument that can image the pet signal and image fluorescence with subcellular resolution (see figure of multicolor hela cells). multiple instruments are required to image pet, whole organ fluorescence, and single cell fluorescence with sub-cellular resolution.