Optimized cocktail of Y-90/Lu-177 for radionuclide therapy of neuroendocrine tumors of various sizes: a simulation study

Background and objectives There is significant interest and potential in the treatment of neuroendocrine tumors via peptide receptor radionuclide therapy (PRRT) using one or both of Y-90 and Lu-177-labeled peptides. Given the presence of different tumor sizes in patients and differing radionuclide dose delivery properties, the present study aims to use Monte Carlo simulations to estimate S-values to spherical tumors of various sizes with Y-90 and Lu-177 separately and in combination. The goal is to determine ratios of Y-90 to Lu-177 that result in the largest absorbed doses per decay of the radionuclides and the most suitable dose profiles to treat tumors of specific sizes. Material and methods Particle transfer calculations and simulations were performed using the Monte Carlo GATE simulation software. Spherical tumors of different sizes, ranging from 0.5 to 20 mm in radius, were designed. Activities of Lu-177 and Y-90, individually and in combination, were homogeneously placed within the total volume of the tumors. We determined the S-values to the tumors, and to the external volume outside of the tumors (cross-dose) which was used to approximate background tissue. The dose profiles were obtained for each of the different tumor sizes, and the uniformity of dose within each tumor was calculated. Results For all tumor sizes, the self-dose and cross-dose per decay from Y-90 were higher than that from Lu-177. We observed that Lu-177 had the most uniform dose distribution within tumors with radii less than 5 mm. For tumors greater than 5 mm in radius, a ratio of 25% Y-90 to 75% Lu-177 resulted in the most uniform doses. When the ratio of Lu-177 to Y-90 was smaller, the uniformity improved more with increasing tumor size. The cross-dose stayed approximately constant for tumors larger than 15 mm for all ratios of Lu-177 to Y-90. Finally, as the size of the tumor increased, differences in the S-values between different ratios of Lu-177 to Y-90 decreased. Conclusion Our work showed that to achieve a more uniform dose distribution within the tumor, Lu-177 alone is more effective for small tumors. For medium and large tumors, a ratio of Y-90 to Lu-177 with more or less Lu-177, respectively, is recommended.