347 - Evaluation of Single-Timepoint 177 Lu-PSMA-617 Dosimetry Platforms for Tumors and Organs at Risk

03:55pm - 04:05pm ET

Room 156

Presenter(s)

Srikrishna Tirumalareddy, BS - Thomas Jefferson University, Philadelphia, PA

S. Tirumalareddy¹, S. Majid², N. Haldar¹, F. Adejolu¹, K. Zarrabi³, E. Gingold⁴, J. W. DiNome¹, F. Mourtada¹, and L. J. Wilson¹; ¹Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, ²Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, ³Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, ⁴Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA

Purpose/Objective(s):

Lutetium-based radiopharmaceuticals are emerging as a transformative approach to treating metastatic cancer. However, lack of standardization in single-timepoint (STP) dosimetry workflows may limit multi-institutional collaboration and impede shared clinical insight. This study aimed to evaluate STP dose variability across 4 platforms in ¹⁷⁷Lu-PSMA-617 patients.

Materials/Methods:

Patients received up to six 7.4 GBq cycles of ¹⁷⁷Lu-PSMA-617, with quantitative SPECT imaging acquired 72 hours post-cycle for up to 3 cycles. Volumes of interest (VOIs) included tumors, manually contoured and reviewed by a radiation oncologist, and the kidneys and parotids, auto-contoured with a validated tool (ProtegeAI, MIM). We performed STP dose calculations in 4 platforms: a MIRD-based organ-level approach (MIRD; MIRDcalc), a commercial Voxel S-Value system (VSV-C; MIM SurePlan MRT), a commercial Monte Carlo model (MC; Voximetry Torch), and an open-source Voxel S-Value tool (VSV-O; OpenDose3D). Madsen time integration was used in all platforms, except for VSV-C, which used the Hanscheid method. We evaluated tumor dosimetry in the 5 largest tumors per patient to focus on dominant lesions. Repeated Measures ANOVA with Bonferroni-corrected post hoc t-tests assessed differences between platforms (a = 0.05). Linear Mixed-Effects Models (LMEs) tested inter-patient and inter-platform variability, quantified by standard deviations (SDs).

Results:

We calculated kidney and parotid absorbed doses for 36 cycles over 27 patients, and 53 tumors across 10 patients over 13 cycles. Mean MIRD doses ± SDs (Gy) were 2.0 ± 0.7, 1.7 ± 1.1, and 9.9 ± 11.2 for kidneys, parotids, and tumors respectively. Doses significantly differed across platforms in all VOIs (ANOVA p = 2E-8). Bonferroni-corrected post hoc tests yielded significant differences in kidney doses between all platforms (p = 0.01). Parotid doses significantly differed across all platforms (p = 0.02), except for VSV-C, which did not differ from MIRD or VSV-O. For tumor doses, VSV-O differed from VSV-C and MIRD (p = 0.03), and MIRD differed from MC (p=0.04). All other comparisons were not significant. LME inter-patient SDs (Gy) were 0.7, 1.1, and 5.5, while inter-platform SDs were 0.1, <0.1, and 0.6, for kidneys, parotids, and tumors respectively.

Conclusion:

We evaluated STP kidney, parotid, and tumor doses following ¹⁷⁷Lu-PSMA-617 in 4 platforms and found statistically significant differences between platforms in all VOIs, but SDs were small, suggesting limited clinical relevance. Furthermore, inter-patient variability dominated inter-platform variability in all VOIs. Tumor doses showed the greatest variability across patients, underscoring the need for personalized activity administration. Small inter-platform variability supports STP dosimetry as a reliable approach and encourages shared clinical insight, improving patient care.