Tumor Cure Probability During α-RIT of Ovarian Cancer with Different Radiation Sensitivity

Abstract

Purpose: To calculate the tumor cure probability (TCP) and metastatic cure probability (MCP) during α-radioimmunotherapy (α-RIT) of small ovarian cancer tumors with cells of different radiation sensitivity. Materials and Methods: 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 D₃₇, of the tumor cells. The calculations were performed using various assumptions regarding the activity distribution in measured tumors and used the α-particle energies emitted from astatine-211 (²¹¹At). 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. Results: In the case of a maximum diffusion depth of 30 μm for the activity in the tumors, the TCP was high for D₃₇ values not exceeding ~4.3, ~2.9, ~1.8, and ~0.8 Gy for 200, 100, 50, and 25 kBq ²¹¹At-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 D₃₇ value should not exceed ~2.2, ~1.3, ~0.6, and ~0.3 Gy when injecting 200, 100, 50, or 25 kBq, respectively, assuming a maximum diffusion depth of 30 μm for the activity in the tumors. Conclusion: The radiation sensitivity, expressed as D₃₇, of tumor cells subjected to α-RIT could be decisive for therapeutic outcome, expressed as TCP or MCP, when treating small tumors of ovarian cancer.