Fig. 1
Strategy for PET-based cell tracking with the R26-mT/sr39tk mouse line. a Generation of experimental animals for PET imaging. R26-mT/sr39tk mice carry the Cre-activatable R26-mT/sr39tk transgene that has been integrated via homologous recombination into the Rosa26 (R26) locus. In R26-mT/sr39tk mice, sr39tk expression is blocked by a loxP-flanked (triangles) gene cassette encoding membrane-targeted tandem dimer tomato red fluorescent protein (mT). R26-mT/sr39tk mice are mated with mice that express Cre (or CreERT2) under control of a cell type-specific promoter (e.g., Pf4, CD4 or Myh6). In progeny mice, Cre recombination activates sr39tk expression in the respective target cell population (blue shaded oval) as shown in detail in b. b Strategy for Cre-dependent sr39tk expression and labeling of distinct cell types. The R26-mT/sr39tk L2 allele (carrying two loxP sites) encodes sr39tk preceded by a loxP-flanked (triangles) sequence encoding the mT protein. From the L2 allele, mT but not sr39tk is expressed. In cells expressing Cre recombinase, the mT cassette is removed and thereby the L2 allele is converted to the L1 allele (carrying one loxP site), from which sr39tk is expressed under control of the ubiquitous CAG promoter. Sr39tk phosphorylates the tracer molecule [18F]FHBG, which cannot leave the cell once phosphorylated. [18F]FHBG accumulation in sr39tk-expressing cell populations allows their in vivo detection by PET imaging. See also Supplementary Fig. 1
