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Figure 1 Diagrams of detection of (A) enzyme-based (e.g., herpes simple virus type 1 thymidine kinase [HSV1-tk]), (B) receptor-based (e.g., dopamine type 2 receptor [D2R]), and (C) transporter-base (e.g., sodium-iodide symporter [NIS]) reporter genes detected by positron emission tomography using F-18–labeled tracers or by single-photon emission tomography using I-123 (reprinted from Acton and Zhou [44] with permission from Edizioni Minerva Medica). In A, 9-[3-fluoro-1-hydroxy-2-(propoxymethyl)]guanine tracers that are bound and metabolized by the HSV1-TK will be trapped inside the cells, whereas unbound ones will diffuse out of cells. In B, tracers binding to D2R on cell surface will contribute to the imaging signal, whereas unbound ones will be washed out. In C, tracers will be transported into and out of cells by NIS; cells from nonthyroid tissues, however, cannot retain the iodine inside through organification (see the section "Radionucleotide Imaging" for details). (D) In vivo assessment of cell survival and proliferation over time. Ten million (10⁷) murine embryonic stem cells transfected with a truncated version of HSV1-tk were injected into the myocardium of a noninfarcted nude rat; positron emission tomography was performed at day 4 and weeks 1, 2, 3, and 4. Approximately 1 mCi [F-18]9-[3-fluoro-1-hydroxy-2-(propoxymethyl)]guanine was injected intravenously for visualization of HSV1-tk–expressing cells. Positive signal was observed at week 1 in animals receiving cells, but control animals had background activities only. Quantification of imaging signals showed a drastic increase of thymidine kinase activity from week 2 to week 4, corresponding to proliferation of embryonic stem cells into intracardiac and extracardiac tumors, that is, teratoma (reprinted from Cao et al. [45] with permission).