Therapeutic efficacy of α-radioimmunotherapy with different activity levels of the 213Bi-labeled monoclonal antibody MX35 in an ovarian cancer model

Abstract

BackgroundThe aim of this study was to compare the therapeutic efficacy of two different activity levels of the 213Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of 213Bi-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy. Body weight and white blood cell counts were monitored after treatment for possible signs of toxicity.ResultsThe tumor-free fraction of the animals treated with 3 MBq/mL of 213Bi-MX35 was 0.55, whereas that of animals treated with 9 MBq/mL of 213Bi-MX35 was 0.78. The control group treated with unlabeled MX35 had a tumor-free fraction of 0.15. No significant reduction in white blood cell counts or weight loss was observed.ConclusionsTumor growth after i.p. treatment with 213Bi-MX35 was significantly reduced compared to treatment with unlabeled MX35. Treatment with 9 MBq/mL of 213Bi-MX35 resulted in higher tumor-free fraction compared with 3 MBq/mL of 213Bi-MX35, but this difference was not statistically significant. No signs of toxicity were observed in the treated animals.

Therapeutic Efficacy of 213Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer

“…These radiopharmaceuticals have shown therapeutic efficacy in cancer indications such as multiple myeloma, 46,47 leukemia, 48,49 non-Hodgkin's lymphoma, 50 and disseminated ovarian cancer. 51 In this study, the bifunctional chelator p-SCN-Bn-CHX-A″-DTPA was conjugated to 2Rs15d, which resulted in a reproducible mixture of conjugates with an average of one DTPA-chelators per sdAb. After radiolabeling, the resulting radio-conjugate proved to be stable in the final buffer at 25 and 37 °C.…”

“…Until now, most preclinical and clinical studies reported make use of mAbs and peptides as targeting vehicles in combination with 213 Bi. These radiopharmaceuticals have shown therapeutic efficacy in cancer indications such as multiple myeloma, , leukemia, , non-Hodgkin’s lymphoma, and disseminated ovarian cancer …”

Ra‐224 labeling of calcium carbonate microparticles for internal α‐therapy: Preparation, stability, and biodistribution in mice

“…When proposing use of an internal α‐emitter for cancer treatment, it is important to choose a radionuclide with physical properties apt for the application. Intraperitoneal therapy with α‐emitters has shown significant potential in murine models previously, mainly with short‐lived nuclides coupled to monoclonal antibodies . With longer lived nuclides, an unfavorable biodistribution in mice without tumors was found after IP injection of 227 Th coupled to trastuzumab .…”

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

“…Ovarian cancer [101] Bi-DTPA-PAN-622-mAb A pilot therapy study with 213 Bi-DTPA-PAN-622 demonstrated a significant effect on the primary tumor.…”