Table 5.
Promising PET reporter gene strategies.
| Name | Type | Properties | Tracer / substrate | Excretion | Limitations | Ref |
|---|---|---|---|---|---|---|
| Somatostatin receptor type 2 (SSTr2) | Cell surface receptor | G protein-coupled receptor (GPCR). | [68Ga]Ga‑DOTATOC, [68Ga]Ga‑DOTATATE.& | Renal | Endogenous expression in brain, adrenal glands, kidneys, spleen, stomach and many tumours (i.e. SCLC, pituitary, endocrine, pancreatic, paraganglioma, medullary thyroid carcinoma, pheochromocytoma); tracers may cause cell signalling and change proliferation. | 184-187 |
| Dopamin receptor (D2R) | Cell surface receptor | GPCR; tracers cross BBB. | [18F]FESP, [11C]C-Raclopride, [11C]C-N-methylspiperone. | Renal and hepatobiliary | Slow clearance of [18F]FESP; high background in the pituitary gland and striatum due to endogenous expression. | 188-191 |
| Sodium iodide symporter (NIS) | Transporter | Symports sodium ions. | [124I]I-, [18F]BF4-, [18F]SO3F-, [18F]PF6-.& | Renal | NIS is endogenously expressed in thyroid, stomach, lacrimal, salivary and lactating mammary glands, small intestine, choroid plexus, testicles; tracers do not cross BBB. | 192-196 |
| Dopamin transporter (DAT) | Transporter | NaCl-dependent; tracers cross BBB. | [11C]CFT, [11C]C-PE2I, [18F]FP-CIT.& | Renal and hepatobiliary | Data about DAT use as reporter gene are scarce while tracers are widely used. | Patent by 197 |
| Pyruvate kinase M2 | Enzyme | Expression during development; in cancers. Tracer crosses BBB. | [18F]F-DASA-23 | Renal and hepatobiliary | Background in organs of excretion route. | 198 |
| Human thymidine kinase (hmtk2/hΔTK2) | Enzyme | Kinase causing cellular tracer trapping. | [124I]I-FIAU**, [18F]FEAU, [18F]FMAU (hTK2-N93D/L109F). | Renal | Tracers do not cross the BBB; Endogenous signals in gall bladder, intestine and organs involved in clearance. | 160 |
| Deoxycytidine kinase (hdCK) | Enzyme | Kinase causing cellular tracer trapping. | [124I]I-FIAU**, [18F]FEAU. | Renal | Tracers do not cross the BBB; Endogenous signals in gall bladder, intestine and organs involved in clearance. | 141, 161 |
| Glutamate carboxypeptidase 2 (PSMA) | Cell surface enzyme | High expression in prostate. | [18F]F-DCFPyL, [18F]F-DCFBC, [68Ga]Ga-PSMA-11.& | Renal | Background in organs of excretion route; tracers do not cross BBB. | 199 |
| Estrogen receptor α ligand binding domain | Artificial cell surface molecule | No physiological function reported; tracer crosses BBB. | [18F]FES. | Renal and hepatobiliary | 200 |