Tumor cure probability during alpha-RIT of ovarian cancer with different radiation sensitivity

To calculate the tumor cure probability (TCP) and metastatic cure probability (MCP) during alpha-radioimmunotherapy (alpha-RIT) of small ovarian cancer tumors with cells of different radiation sensitivity.

An in-house-developed biokinetic model and a Monte-Carlo program were used to calculate the cumulative activity on tumor cell surfaces and the specific energy to tumor cell nuclei, respectively. An in-house-developed computational model was used to calculate the TCP and MCP as a function of assumed radiation sensitivities, expressed as D(37), of the tumor cells. The calculations were performed using various assumptions regarding the activity distribution in measured tumors and used the alpha-particle energies emitted from astatine-211 ((211)At). Regarding the calculations of the cumulative activity on each cell surface, the number of antigenic sites expressed by NIH:OVCAR-3 cells for the mAb MX35 F(ab')2 was used. To illustrate the tumor growth at the peritoneum in nude mice, scanning electron microscopy images were used.

In the case of a maximum diffusion depth of 30 mum for the activity in the tumors, the TCP was high for D(37) values not exceeding approximately 4.3, approximately 2.9, approximately 1.8, and approximately 0.8 Gy for 200, 100, 50, and 25 kBq (211)At-MX35 F(ab')2 four weeks after cell inoculation, respectively. In order to achieve complete remission of the metastatic disease in mice (i.e. MCP=1), the D(37) value should not exceed approximately 2.2, approximately 1.3, approximately 0.6, and approximately 0.3 Gy when injecting 200, 100, 50, or 25 kBq, respectively, assuming a maximum diffusion depth of 30 mum for the activity in the tumors.

The radiation sensitivity, expressed as D(37), of tumor cells subjected to alpha-RIT could be decisive for therapeutic outcome, expressed as TCP or MCP, when treating small tumors of ovarian cancer.