Intraperitoneal alpha therapy with Ra-labeled microparticles combined with chemotherapy in an ovarian cancer mouse model.
(2022) Frontiers in Medicine — Vol. 10, n° 9, p. 995325 (2022)
Files
fmed-09-995325.pdf
Open Access - Adobe PDF
- 2.94 MB
Details
- Authors
- Abstract
- A novel alpha-therapy consisting of Ra-labeled calcium carbonate microparticles (Ra-CaCO-MP) has been designed to treat micrometastatic peritoneal disease via intraperitoneal (IP) administration. This preclinical study aimed to evaluate its efficacy and tolerability when given as a single treatment or in combination with standard of care chemotherapy regimens, in a syngeneic model of ovarian cancer in immune competent mice. Female C57BL/6 mice bearing ID8-fLuc ovarian cancer were treated with Ra-CaCO-MP 1 day after IP tumor cell inoculation. The activity dosages of Ra ranged from 14 to 39 kBq/mouse. Additionally, Ra-CaCO-MP treatment was followed by either carboplatin (80 mg/kg)-pegylated liposomal doxorubicin (PLD, 1.6 mg/kg) or carboplatin (60 mg/kg)-paclitaxel (10 mg/kg) on day 14 post tumor cell inoculation. All treatments were administered via IP injections. Readouts included survival, clinical signs, and body weight development over time. There was a slight therapeutic benefit after single treatment with Ra-CaCO-MP compared to the vehicle control, with median survival ratios (MSRs) ranging between 1.1 and 1.3. The sequential administration of Ra-CaCO-MP with either carboplatin-paclitaxel or carboplatin-PLD indicated a synergistic effect on overall survival at certain Ra activities. Moreover, the combinations tested appeared well tolerated in terms of weight assessment in the first 4 weeks after treatment. Overall, this research supports the further evaluation of Ra-CaCO-MP in patients with ovarian cancer. However, the most optimal chemotherapy regimen to combine with Ra-CaCO-MP should be identified to fully exploit its therapeutic potential.
- Affiliations
Citations
Wouters, R., Westrøm, S., Berckmans, Y., Riva, M., Ceusters, J., Bønsdorff, T. B., Vergote, I., & Coosemans, A. (2022). Intraperitoneal alpha therapy with Ra-labeled microparticles combined with chemotherapy in an ovarian cancer mouse model. Frontiers in Medicine, 10(9), 995325. https://doi.org/10.3389/fmed.2022.995325 (Original work published 2022)