Table 1. . Key reports on the anticancer efficacy of 3-bromopyruvate in vivo.
| Study (year) | Tumor model | Objective | Treatment with 3-BrPA | Outcomes | Toxicities | Ref. |
|---|---|---|---|---|---|---|
| Geschwind et al. (2002) | VX2 rabbits (n = 22) | Efficacy and feasibility | IA: infusion (compared with embolization) | Histopathology: complete necrosis of treated tumors | Histopathology: no effects on surrounding liver parenchyma | [63] |
| All animals had developed lung metastases that were successfully treated with systemic 3-BrPA | ||||||
| Embolization caused severe peripheral liver necrosis | ||||||
| Vali et al. (2007) | VX2 rabbits (n = 8+30) | Dose-escalation | IA: dose-escalation; single vs serial bolus injection vs 1 h infusion (compared with controls) | Maximum tolerated dose: 25 ml | Histopathology: peripheral liver necrosis at maximum dose | [64] |
| Recommended therapeutic dose = 1.75 ml | ||||||
| Favorable method of delivery = continuous 1 h infusion | ||||||
| Vali et al. (2008) | VX2 rabbits (n = 60) | Biodistribution and efficacy (14c-labeled 3-BrPA) | IA vs IV (compared with controls) | IA: 14c-labeled 3-BrPA accumulated selectively within the tumor | No nontarget distribution of 3-BrPA | [65] |
| IA: FDG-PET showed reduced uptake, prolonged survival (55 vs 18.6 days controls) | No altered FDG uptake in healthy tissue | |||||
| IV: no significant differences in FDG uptake | ||||||
| Vossen et al. (2008) | VX2 rabbits (n = 20) | Efficacy and feasibility of metastatic VX2 tumor model | IA: infusion vs partial hepatectomy vs TACE | VX model is feasible to investigate drug influence on metastatic profile | N.A. | [68] |
| Less abdominal dissemination and kidney metastases compared with both TACE and surgery | ||||||
| All animals developed lung metastases | ||||||
| Liapi et al. (2011) | VX2 liver tumor model in rabbitxenografts (n = 23) | Effects of 3-BrPA on tumor metabolism imaged with FDG-PET | IA vs control | FDG uptake was reduced 7days after therapy | N.A. | [69] |
| Histopathology revealed tumor necrosis confirming imaging results | ||||||
| Ganapathy et al. (2012) | subcutaneous HCC model in mice (Hep 3B cells) (n = 24) | Efficacy and mechanistic analysis | Percutaneous intratumoral injections (for 3 days) (compared with shRNA and controls) | Decreased BLI signal 3 days after treatment | N.A. | [67] |
| Inhibition of tumor progression, induction of apoptosis, inhibition of GAPDH activity | ||||||
| Ota et al. (2013) | orthotopic pancreatic cancer model in mice (Panc-1 cells) (n = 13) | Efficacy, safety and establishment of a new tumor model | US-guided percutaneous intratumoral injections, (compared with controls) | Weekly us measurement and histology after 4 weeks: 1 animal progressed, 5 tumors decreased in size | Ex vivo: no signs of toxicity in pancreas or other organs | [62] |
| Chapiro et al. (2014) | orthotopic pancreatic cancer model in mice (MiaPaCa2 cells) | Feasiblity, efficacy, safety (microencapsulated 3-BrPA) | Daily intraperitoneal injections (compared with gemcitabine and free 3-BrPA) | Establishment of microrencapsulated 3-BrPA for systemic delivery | Ex vivo: no signs of toxicity in other organs | [70] |
| Inhibition of tumor progression on weekly BLI scans | No acute adverse events | |||||
| Histopathology: tumor necrosis | No deaths in contrast to free 3-BrPA | |||||
BLI: Bioluminescence; 3-BrPA: 3-Bromopyruvate; FDG: 18F-2-Deoxy-D-glucose; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; HCC: Hepatocellular Carcinoma, IA: intra-arterial; IV: Intravenous; PET: Positron emission tomography; TACE: Transarterial chemoembolization; US: Ultrasound; VX2 Rabbits: VX2 Liver-Implanted Tumor Model In Rabbits.