Can 177Lu-DOTATATE Kidney Absorbed Doses be Predicted from Pretherapy SSTR PET? Findings from Multicenter Data

Thu, 22 May 2025 00:00:00 +0000

Before performing ¹⁷⁷Lu-DOTATATE therapy for neuroendocrine tumors, somatostatin receptor (SSTR) PET imaging is currently used to confirm sufficient tumor SSTR expression, but it also has potential to be used to personalize treatment by predicting absorbed doses to critical organs. This study aims to validate the predictive capability of SSTR PET in anticipating renal absorbed dose in the first cycle of ¹⁷⁷Lu-DOTATATE using a multicenter dataset to analyze and derive insights from a broader patient population.

Methods: Retrospective data from 5 centers were included in this study: 1 in Canada (n = 25), 1 in Norway (n = 75), 1 in Sweden (n = 18), and 2 in the United States (n = 36 and n = 26). At each center, pretherapy SSTR PET/CT imaging and postcycle 1 ¹⁷⁷Lu imaging-based dosimetry were performed according to site-specific protocols. The mixed-effects model treating centers as random effects was developed using baseline SSTR PET renal uptake values to predict renal absorbed dose from ¹⁷⁷Lu-DOTATATE. Additionally, leave-one-center-out cross-validation and leave-one-sample-out cross-validation were implemented for external and internal validation, respectively, measuring mean absolute error and mean relative absolute error.

Results: Across all participating centers, the median cycle 1 renal absorbed dose was 0.56 Gy/GBq (range, 0.14-1.27 Gy/GBq), whereas the median pretherapy SSTR PET renal uptake was 110.7 Bq/mL/MBq (range, 28.6-287.7 Bq/mL/MBq). The differences among center means were statistically significant for both absorbed dose and PET uptake (P < 0.0001 from 1-way ANOVA). A significant (P < 0.05) correlation was observed between kidney SSTR PET uptake and ¹⁷⁷Lu-DOTATATE absorbed dose for each center (center-specific coefficient of determination ranged from 0.14 to 0.53). When data across all centers were aggregated, the mixed-effects model achieved a coefficient of determination of 0.25 (P < 0.01), resulting in an mean absolute error of 0.15 Gy/GBq (SD, 0.11 Gy/GBq) and an mean relative absolute error of 28% (SD, 24%) for external validation and 0.12 Gy/GBq (SD, 0.10 Gy/GBq) and 22% (SD, 20%) for internal validation.

Conclusion: The correlations observed between SSTR PET renal uptake and ¹⁷⁷Lu-DOTATATE absorbed dose to kidneys across a multicenter population are statistically significant yet modest. The prediction model achieved a mean relative absolute error 28% or less for both external and internal validation of PET-predicted absorbed doses. The intercenter differences suggest the need for standardized imaging protocols and dosimetry workflows.

SPECT/CT Image-Derived Absorbed Dose to Red Marrow Correlates with Hematologic Toxicity in Patients Treated with [177Lu]Lu-DOTATATE

Wed, 01 May 2024 00:00:00 +0000

Hematologic toxicity, although often transient, is the most common limiting adverse effect during somatostatin peptide receptor radionuclide therapy. This study investigated the association between Monte Carlo-derived absorbed dose to the red marrow (RM) and hematologic toxicity in patients being treated for their neuroendocrine tumors.

Methods: Twenty patients each receiving 4 treatment cycles of [¹⁷⁷Lu]Lu-DOTATATE were included. Multiple-time-point ¹⁷⁷Lu SPECT/CT imaging-based RM dosimetry was performed using an artificial intelligence-driven workflow to segment vertebral spongiosa within the field of view (FOV). This workflow was coupled with an in-house macroscale/microscale Monte Carlo code that incorporates a spongiosa microstructure model. Absorbed dose estimates to RM in lumbar and thoracic vertebrae within the FOV, considered as representations of the whole-body RM absorbed dose, were correlated with hematologic toxicity markers at about 8 wk after each cycle and at 3- and 6-mo follow-up after completion of all cycles.

Results: The median of absorbed dose to RM in lumbar and thoracic vertebrae within the FOV (D _{median,vertebrae}) ranged from 0.019 to 0.11 Gy/GBq. The median of cumulative absorbed dose across all 4 cycles was 1.3 Gy (range, 0.6-2.5 Gy). Hematologic toxicity was generally mild, with no grade 2 or higher toxicity for platelets, neutrophils, or hemoglobin. However, there was a decline in blood counts over time, with a fractional value relative to baseline at 6 mo of 74%, 97%, 57%, and 97%, for platelets, neutrophils, lymphocytes, and hemoglobin, respectively. Statistically significant correlations were found between a subset of hematologic toxicity markers and RM absorbed doses, both during treatment and at 3- and 6-mo follow-up. This included a correlation between the platelet count relative to baseline at 6-mo follow up: D _{median,vertebrae} (r = -0.64, P = 0.015), D _{median,lumbar} (r = -0.72, P = 0.0038), D _{median,thoracic} (r = -0.58, P = 0.029), and D _{average,vertebrae} (r = -0.66, P = 0.010), where D _{median,lumbar} and D _{median,thoracic} are median absorbed dose to the RM in the lumbar and thoracic vertebrae, respectively, within the FOV and D _{average,vertebrae} is the mass-weighted average absorbed dose of all vertebrae.

Conclusion: This study found a significant correlation between image-derived absorbed dose to the RM and hematologic toxicity, including a relative reduction of platelets at 6-mo follow up. These findings indicate that absorbed dose to the RM can potentially be used to understand and manage hematologic toxicity in peptide receptor radionuclide therapy.

Ka Kit Wong | Theragnostic Imaging

Can 177Lu-DOTATATE Kidney Absorbed Doses be Predicted from Pretherapy SSTR PET? Findings from Multicenter Data

SPECT/CT Image-Derived Absorbed Dose to Red Marrow Correlates with Hematologic Toxicity in Patients Treated with [177Lu]Lu-DOTATATE