In:
Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-10-10)
Abstract:
A novel alpha-therapy consisting of 224 Ra-labeled calcium carbonate microparticles ( 224 Ra-CaCO 3 -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 224 Ra-CaCO 3 -MP 1 day after IP tumor cell inoculation. The activity dosages of 224 Ra ranged from 14 to 39 kBq/mouse. Additionally, 224 Ra-CaCO 3 -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 224 Ra-CaCO 3 -MP compared to the vehicle control, with median survival ratios (MSRs) ranging between 1.1 and 1.3. The sequential administration of 224 Ra-CaCO 3 -MP with either carboplatin-paclitaxel or carboplatin-PLD indicated a synergistic effect on overall survival at certain 224 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 224 Ra-CaCO 3 -MP in patients with ovarian cancer. However, the most optimal chemotherapy regimen to combine with 224 Ra-CaCO 3 -MP should be identified to fully exploit its therapeutic potential.
Type of Medium:
Online Resource
ISSN:
2296-858X
DOI:
10.3389/fmed.2022.995325
DOI:
10.3389/fmed.2022.995325.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2775999-4
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