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. 2020 Apr 3;11:154. doi: 10.3389/fphys.2020.00154

TABLE 1.

Reporter gene classes according to their molecular imaging mechanisms (cf. Figure 4) including selected examples.

Mechanism [cf. Figure 4] Reporter Properties Matching imaging modality References
Transporter [a] Mammalian transporters Sodium iodide symporter (NIS, SLC5A5); Norepinephrin transporter (NET, SLC6A2); Dopamine transporter (DAT, SLC6A3). Various radiotracers for PET and SPECT for all reporters listed. (Dai et al., 1996; Moroz et al., 2007; Jauregui-Osoro et al., 2010; Khoshnevisan et al., 2016, 2017; UCL Business PLC, 2017; Jiang et al., 2018)
Ion transporter from magnetotatic bacteria MS-1 magA. MRI (Endogenous or exogenous iron). (Nakamura et al., 1995; Zurkiya et al., 2008; Cho et al., 2014)
Polypeptides Sodium-Taurocholate Co-transporting Polypeptide (NTCP). Fluorescence and MRI. (Wu et al., 2019)
Cell surface protein binding [b] G-protein-coupled receptors Somatostatin receptor type 2 (SSTR2); Dopamine receptor (D2R). PET and SPECT radiotracers available; PET radiotracers available. (Satyamurthy et al., 1990; MacLaren et al., 1999; Rogers et al., 1999, 2000; Zinn et al., 2000a; Chaudhuri et al., 2001; Liang et al., 2001; Hwang et al., 2007)
Recycling receptor Transferrin receptor. MRI (SPIO). (Weissleder et al., 2000)
Cell-surface antigen-based reporter Human carcino-embryonic antigen-based reporters are recombinant proteins based on CEA minigene (N-A3) fused to extracellular and transmembrane domains of human FcγRIIb receptor, CD5 or TfR carboxyterminal domain. PET and SPECT radiotracers available. (Hammarstrom, 1999; Hong et al., 2008; Kenanova et al., 2009; Barat et al., 2011; Girgis et al., 2011)
Mammalian cell surface protein PSMA and mutants; radiotracers bind to the protein using it as a cell surface protein and not exploiting its enzymatic properties. PET and SPECT radiotracers available. (Castanares et al., 2014; Minn et al., 2019)
Enzymes [ci] Bacterial enzymes E. coli dihydrofolate reductase (eDHFR); E. coli β-galactosidase. PET; Various including OPTICAL (chemiluminescence), MRI, PET and SPECT. (Fowler and Zabin, 1977; Louie et al., 2000; Li et al., 2007; Liu and Mason, 2010; Green et al., 2017; Sellmyer et al., 2017, 2019; Guo et al., 2019; Krueger et al., 2019)
Mammalian and non-viral kinases Pyruvate kinase M2, thymidine kinases (viral such as HSV1-tk and mammalian variants), deoxycytodine kinases. Various PET tracers for the individual kinases. (Tjuvajev et al., 1995; Ponomarev et al., 2007; Jang et al., 2010, 2012; Likar et al., 2010; Park et al., 2015; Lee et al., 2017; Haywood et al., 2019; Seo et al., 2019).
Other mammalian enzymes Tyrosinase PAT/MSOT, MRI, PET. (Weissleder et al., 1997; Ponomarev et al., 2004; Krumholz et al., 2011)
Luciferases Various luciferases including Firefly, Green Click Beetle; Gaussia, Renilla; and NanoLuc. OPTICAL (bioluminescence): Firefly, Green Click Beetle: D-luciferin; Gaussia, Renilla: coeloenterazine; NanoLuc: imidazopyrazinone. (Lorenz et al., 1991; Loening et al., 2006; Tannous, 2009; Inoue et al., 2011; Hall et al., 2012; Schaub et al., 2015; Germain-Genevois et al., 2016; La Barbera et al., 2017; Mezzanotte et al., 2014, 2017; Hunt et al., 2016; Aswendt et al., 2019; Weihs and Dacres, 2019; Zhang et al., 2019)
Fluorescent Proteins [cii] Proteins with intrinsic fluorophores Red fluorescent: E2-Crimson/mTagRFP/mPlum/mNeptune; Infrared fluorescent: iRFP 670/iRFP 720. OPTICAL (fluorescence upon appropriate excitation): (emission λmax): 543/584/649/650; (emission λmax): 670/720. (Merzlyak et al., 2007; Kremers et al., 2009; Lin et al., 2009; Filonov et al., 2011; Liu et al., 2013; Shcherbakova and Verkhusha, 2013; Deliolanis et al., 2014; Isomura et al., 2017; Zhou et al., 2018; Fukuda et al., 2019)
Frequency-selective contrast/other Artificial protein Contrast based on transfer of radiofrequency labeling from the reporter’s amide protons to water protons. MRI (CEST). (Gilad et al., 2007; Farrar et al., 2015)
Formation of gas vesicles/other Mammalian acoustic reporter gene (mARG) Gas vesicles are produced which generate US contrast. US (3.2 MPa insonation). (Farhadi et al., 2019)