Table 2.
PET reporter gene/probe systems
| Reporter Gene | Reporter Probe | Advantages | Disadvantages |
|---|---|---|---|
| 1. Reporter Genes Potentially Immunogenic in Humans | |||
| Herpes Simplex Virus thymidine kinase (HSV1-tk) and mutants: HSV1-sr39tk, HSV1-A167Ysr39tk, HSV1-A167Ytk, HSV1-A168Htk, HSV1-R176Qtk, Destabilized HSV1-tk |
[18F]FHBG [18F]FEAU [124I]FIAU |
1. Relatively high sensitivity 2. Most validated PET reporter gene/probe system 3. Absence of reporter gene in normal mammalian cells 4. Several PRPs with good pharmacokinetics 5. FDA IND approved PRP ([18F]FHBG) 6. Dual purpose IRG and suicide gene |
1. Available probes don't cross the BBB 2. High activity in organs involved in clearance 3. Deiodination of the radio-iodine labeled probes 4. Possible perturbation of cell characteristics like all other reporter genes |
| Varicella-Zoster Virus Thymidine Kinase (VZV-tk) | [18F or 11C]BCNA | Probes specific for VZV-tk and not HSV1-tk | BCNA did not cross BBB |
| LacZ | [11C] β-galactosyl triazoles |
Probes not specific for LacZ | |
| 2. Reporter Genes Less Likely to be Immunogenic in Humans | |||
| Modified human mitochondrial thymidine kinase (hmTK2) and optimized mutants | [18F]FEAU [124I]FIAU, [18F]L-FMAU |
1. Dual purpose RG and suicide gene 2. Available RPs with good pharmacokinetics 3. May be used in patients receiving Penciclovir |
1. Currently, lower sensitivity than HSV1-tk and mutants 2. Available probes don't cross the BBB 3. High activity in organs involved in clearance 4. Deiodination of the radio-iodine labeled probes 5. Possible perturbation of cell characteristics like all other reporter genes |
| Truncated mutant deoxycytidine kinase (h∆dCKDM) | [18F]FEAU | 1. May be used in patients receiving Penciclovir | 1. Probe doesn't cross the BBB 2. Possible perturbation of cell characteristics like all other reporter genes |
| Dopamine 2 Receptor (D2R) Mutant D2R |
[18F]FESP Also potentially: [11C]Raclopride [11C]N-methylspiperone |
1. Non-mutated human gene is not immunogenic 2. [18F]FESP can be used in humans and has good pharmacokinetics 3. Probe can cross BBB 4. Binding of FESP to mutant D2R does not cause signal transduction |
1. High background in Pituatory and Striatum 2. Long wait time for [18F]FESP clearance |
| Human estrogen receptor α ligand binding domain (hERL) | [18F]FES | 1. Probe can cross BBB 2. Probe used in clinic 3. hERL lacks activity as a transcription factor |
1. Estrogen receptor is over-expressed in uterus, ovaries, mammary gland and breast cancer cells |
| Human somatostatin receptor subtype 2 (hSSTr2) | 68Ga-DOTATOC | 1. The PRP has good pharmacokinetics and has already undergone clinical testing | 1. Somatostatin binding to hSSTr2 can cause cell signaling; hence expression may perturb cell characteristics 2. Some tumors and tissues express hSSTr2 |
| Recombinant human carcinoembryonic antigen (CEA) | Iodine-124 labeled Anti-CEA scFv-Fc H310A antibody fragment |
1. Not expressed in normal adult human cells, except for colon lumen | 1. Dehalogenation of probe 2. Naturally overexpressed in carcinomas 3. Long half-life makes unsuitable for dynamic imaging 4. Probe cannot image in CNS |
| Engineered antibody fragments: DAbR1 | 86Y-AABD | 1. Humanized IRG 2. High sensitivity |
1. Possibly immunogenic 2. 86Y is not a good PET radioisotope |
| Humanized membrane anchored anti-polyethylene glycol (PEG) | 124I-PEG-SHPP | 1. A universal IRG allowing imaging by PET, MRI and optical probes 2. PEG is non-toxic and FDA approved |
1. Long half-life of iodine does not allow dynamic imaging of molecular events. 2. Potential deiodination. |
| Sodium Iodide Symporter (NIS) | 124I | 1. Lack of immune reaction 2. Easy to obtain probes 3. Dual purpose as a reporter gene and a therapeutic transgene |
1. Naturally expressed in thyroid, stomach, salivary glands, mammary glands, and sometimes breast cells 2. Probes are not trapped and can efflux, short imaging window |
| Human norepinephrine transporter (hNET) | [124I]MIBG | 1. Probes clinically used | 1. High normal tissue background, since hNET is expressed in many normal tissues 2. Induced hNET expression will likely change cell biological function |