Cycle-dependent variation of tumor absorbed dose rates in<sup>177</sup>Lu-DOTATATE therapies.

Abstract

Purpose.We aimed to evaluate the variability of tumor absorbed dose rate at 24 h post-injection across multiple cycles of177Lu-DOTATATE therapy. Using patient-specific Monte Carlo (MC) simulations, we quantified cycle-dependent variations in tumor absorbed dose rate and explicitly separated self- and cross-irradiation contributions.Methods.Five patients, with neuroendocrine tumor metastases, who received 3-4 cycles of177Lu-DOTATATE therapy with a fixed activity of 7.4 GBq per cycle, were studied. All patients underwent single-photon emission computed tomography imaging 24 h after each injection cycle. The GATE MC framework (version 8.1) was used for voxel-level tumor dosimetry. Dosimetry was performed for 25 individual lesions, giving a total of 92 individual absorbed dose assessments across all cycles. We focused on relative, cycle-to-cycle comparison of tumor self- and cross-absorbed dose rate.Results.The cross-absorbed dose from surrounding tissues comprised a substantial fraction of total tumor absorbed dose rate, up to 32.64% across individual tumors and cycles. Linear mixed-effects analysis across all five patients revealed statistically significant differences in cross-absorbed dose contribution across treatment cycles (F-values: 4.433-24.607;p-values: 0.002-Conclusion.A key finding of our study is that the cross-absorbed dose originating from organs containing or surrounding the tumor can substantially contribute to the absorbed dose rate, a factor that must be considered for accurate estimations at each cycle of treatment. Despite identical injected activities, tumor self- and cross-dose substantially changed over cycles. These results demonstrate the necessity for patient-specific activity administration protocols and cycle-specific dosimetry assessments in177Lu-DOTATATE therapy, supporting a paradigm shift from fixed-activity regimens toward individualized, image-based dosimetry-guided treatment strategies.