Comparison of imaging-based bone marrow dosimetry methodologies and their dose-effect relationships in...

Establishing accurate methods for red marrow (RM) dosimetry is an important step toward patient-specific treatment guidance. We compared image-based dosimetry methods and investigated their role in predicting changes in blood counts following [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (¹⁷⁷Lu RLT).

Four image-based dosimetry methodologies were applied to patients who received 2-bed position serial ¹⁷⁷Lu SPECT/CT after cycle 1 of RLT, with segmentation of all spongiosa within the field-of-view performed on CT using deep learning tools. Cycle 1 RM absorbed doses (ADs) were estimated with: 1) the time-integrated activity (TIA) in segmented spongiosa coupled with MIRD-based S-values (MIRD); 2) the TIA concentration in the segmented aorta (a surrogate for blood-based dosimetry) coupled with MIRD-based S values (MIRD_aorta); 3) the voxel-level TIA map coupled with an in-house Monte Carlo (MC) dosimetry code that incorporated a micro-scale modeling of the spongiosa (MC); and 4) a novel method that utilizes [⁶⁸Ga]Ga-PSMA-11 PET/CT and [^99mTc]Tc-sulfur colloid (SC) SPECT/CT for tumor and marrow localization coupled with the above MC code, modified to allow tumor infiltration of the spongiosa (MC_SC+PET). Spearman rank correlation of AD from the four methods with changes in select blood counts was evaluated.

Imaging data was available for 20 patients for methods 1-3, while SC images were available for 12 patients for method 4. Cycle 1 AD to the FOV RM was, on average, 1.9 Gy (range: 0.1-8.0 Gy) for MIRD, 0.08 Gy (range: 0.01-0.27 Gy) for MIRD_aorta, 2.5 Gy (range: 0.1-10.3 Gy) for MC, and 1.6 Gy (range: 0.1-4.6 Gy) for MC_SC+PET. The ADs from MIRD_aorta were not concordant with MIRD, MC, or MC_SC+PET (|CCC|< 0.01) and were generally underestimates. For 3 patients with high bone tumor burden, MC_SC+PET gave lower average AD than MIRD (39%) and MC (53%), potentially due to more accurate localization of marrow and tumor. Cycle 1 RM ADs were correlated with relative change in blood counts at 6-weeks post-cycle 1 with significant correlation observed for neutrophils with MIRD, MC, and MC_SC+PET with Spearman rank correlations ranging from r = - 0.61 to r = - 0.88 (P < 0.01). Correlation with white blood cells at 6-months was also significant with r = - 0.80 (P < 0.01) for these three methods. MIRD_aorta did not correlate with any acute or chronic changes in blood counts.

The RM AD estimates from the blood-based surrogate were not concordant with the other image-based calculations and did not correlate with changes in blood values. Including patient-specific tumor and marrow distribution information resulted in lower AD for patients with a high bone metastatic burden. These findings have implications for managing hematological toxicities in ¹⁷⁷Lu RLT, especially if dosimetry-guided treatment planning is considered.