Table 5.
Therapies evaluated by PET and/or autoradiography with the MPTP PD model in the last 5 years.
| Species Age | Model Induction Protocol | PET Timepoints | PET Tracer | Therapeutic Intervention |
|---|---|---|---|---|
| Cynomolgus macaques (Macaca fascicularis) 8-14 years old (3.0-4.8 kg) [147] |
Once-daily subcutaneous injection of MPTP (0.2 mg/kg) | N/A | [11C]raclopride | Pridopidine - 3 doses (15, 20, and 30 mg/ kg) |
| Cynomolgus macaques (Macaca fascicularis) Male (chronic low dose) and female (advanced PD) 11.8 ± 0.8 years old (5.2 ± 0.6 kg) [148] |
Early-stage: low doses of MPTP injections (dose range: 0.05-0.25 mg/kg; intravenously) two to three times per week for up to 15 months. Advanced-stage: continuous infusion of MPTP using subcutaneous osmotic mini-pumps (0.5 mg/24 hours) for around 6 months |
N/A | [11C]-PXT012253 | Foliglurax - PXT002331 (in water) was administered at dose levels of 2 and 25 mg/kg as a single dose on days 1 and 8 and twice daily on days 2 through 7 |
| Male C57BL/6 mice 5-8 weeks old (25-35 g) [149] | Intraperitoneally (i.p.) injected with a single daily dose of 25 mg/kg MPTP hydrochloride solution for 5 consecutive days (days 1-5) |
Baseline PET one day before MPTP treatment (day 0), a second PET scan one day before magnolol treatment (day 10), and a third PET scan on the day following the final treatment (day 17) | [18F]DTBZ | Magnolol (10 mL/kg, i.p.) - single daily dose for 6 days after the final MPTP treatment |
| Cynomolgus macaques (Macaca fascicularis) 4 males and 5 females (3.3-8.0 kg) [150] |
Subacute type: MPTP was administered (0.5 mg/kg) for 3 consecutive days and then every 2-3 days while motor signs were monitored (a total of 5-9 days). Subchronic type: MPTP was administered (0.3 mg/kg) for 2 consecutive days and then every 6-8 days while motor signs were monitored (a total of 30-70 days) | N/A | [11C]PE2I | Lentiviral vector therapy (Calbindin) - 1 to 2 months before MPTP was systemically administered |
| Rhesus macaques (Macaca mulatta) 10-14 years old (8-19 kg) [151] |
Unilateral (right) intracarotid artery (ICA) injection of 3-4 mg of neurotoxin MPTP-HCl |
12–18 months post-cell transplantation | [11C]DTBZ | Cell therapy: received induced pluripotent stem cell DA in the basal ganglia ipsilateral to the MPTP ICA injection (right)- 1-3 years after MPTP model induction |
| Rhesus macaques (Macaca mulatta) - 14 males and 2 females 8-22 years old (9.1±1.7 kg for PD and 9.7±2.7 kg) [110] | Chronic intravenous administration of MPTP over several months | The parkinsonian animals were evaluated before and 6-48 months after unilateral striatal implantation | [18F]FDG | Human retinal pigment epithelial cells - hRPE - hRPE-GM or sham (GM only) were implanted unilaterally in the striatum in the fully recovered and stable animals (i.e., motor scores unchanged for 3-4 months) |
| C57BL/6 mice 8 weeks old [152] |
N/A | N/A | [89Zr]hNSCs | Human neural stem cells (hNSCs) - nasal and striatal administration |
| Male Rhesus macaques (Macaca mulatta) 9-13 years old (8-19 kg) [146] |
Unilateral (right) intracarotid artery injection of MPTP | Twenty-four months of follow-up |
[18F]FEPPA | Induced pluripotent stem cell - 3 to 12 months later, the monkeys received injections of allogeneic iPSC-mDA |
| Male Cynomolgus macaques (Macaca fascicularis) 2-3-years-old [153] |
The animals were injected intravenously with MPTP hydrochloride (0.4 mg kg−1 as a free base; Sigma-Aldrich) twice a week until they observed persistent Parkinsonian symptoms | Before, 2 weeks and 1, 3, 6, 12, 18, and 24 months after cell transplantation | [11C]PK11195, [11C]KTP-Me, [18F]FLT | Induced pluripotent stem cell |
| Cynomolgus macaques (Macaca fascicularis) (2.5-3.5 kg) [154] |
Intravenous injections of MPTP HCl (0.4 mg/kg) twice a week until persistent Parkinsonian behavioral symptoms became evident | N/A | [18F]DOPA | Induced pluripotent stem cell |
| C57bl/6J mice 8 weeks old (22.4 ± 0.8 g) [155] | MPTP (15 mg/kg; Sigma- Aldrich, St. Louis, MO, USA) intraperitoneally for 5 consecutive days | Day 0 (baseline; scan 1), day 6 (scan 2), and day 13 (scan 3) | [18F]FE-PE2I | Fas-associated factor 1 inhibitor - KM-819. Oral administration (20 mg/kg) for 6 consecutive days, starting from 48 h after the last dose of MPTP |
| Male cynomolgus macaques (Macaca fascicularis) 2.5 ± 0.1 years old; 3.48 kg ± 0.1 kg) [156] |
Intramuscular injections of 0.25 mg/kg of MPTP for 7 consecutive days, as previously described | Baseline, post-MPTP lesioning, and at 6 months post-vector administration | 6-[18F]-fluoro-L-m-tyrosine | Gene therapy - OXB-102 (a lentiviral vector with an optimized expression cassette for DA biosynthesis) |
| Cynomolgus macaques (Macaca fascicularis) 3-5 years old (4-6 kg) [157] |
Intramuscular MPTP injections (mean total dose of 1.55 mg/kg) | 1) Baseline, 2) after MPTP and just before the first levodopa period (post-MPTP), 3) after the first period of levodopa treatment (post-levodopa1), 4) after a two-month washout period and before MDMA (pre-MDMA), 5) after MDMA and just before the second period of levodopa exposure (post-MDMA) and 6) after the second levodopa period (post-levodopa2) | [11C]PE2I and [11C]DASB | Levodopa-inducing dyskinesia – 2 months after MPTP intoxication, all monkeys received intra-muscular injections of L-3,4-levodopa twice daily for 2 months |
| Rhesus macaques (Macaca mulatta) - 3 females and 2 males 5-7 years old [145] | Weekly doses of intramuscular MPTP (0.2-0.8 mg/kg, Sigma-Aldrich) starting at 0.2 mg/kg for 18 weeks and increasing to 0.8 mg/kg to maintain a parkinsonian state | Baseline and at approximately 8 (PET I), 16 (PET II), 24 (PET III) and 38 weeks (PET IV) after the initiation of MPTP administration | [18F]FEPPA | Tumor necrosis factor (TNF) inhibitor (XPro1595) - At 11 weeks, subcutaneous treatment of XPro1595 (10 mg/kg) started and continued every 3 days |
Abbreviation: N/A – not available.