Personalized therapy planning for 177Lu-DOTATATE using a kidney-driven dose optimization method

Purpose: The current 177Lu-DOTATATE prescription of 4 therapy cycles at 7.4GBq may lead to differential effects on individual patients due to individual biodistribution and tracer kinetics. Sandstrӧm et al [1] and others have hypothesized that post-therapy imaging of 177Lu-DOTATATE can be used to determine the maximum number of therapy cycles delivered to the patient while remaining within organ absorbed dose limits. The current work assesses the use of a voxel-based dose calculation method using serial SPECT/CT images to determine patient-specific kidney tolerance for additional cycles of therapy. Methods: Serial SPECT/CT scans of 3 patients were acquired on a Siemens Symbia Intevo system after standard administration of 7.4 GBq of 177Lu-DOTATATE. Each serial SPECT/CT dataset contained 4 images, one acquired on the day of administration of activity and 3 additional scans acquired at times over the following week. These SPECT/CT scans were quantitatively reconstructed using MIM SPECTRA Quant’s OSEM algorithm including attenuation correction, scatter correction, and resolution recovery. Kidney regions were drawn based on the CT of the first timepoint for each patient. Using the MIM SurePlan MRT package, each CT image was deformably registered to the first timepoint, and SPECT images were co-registered. Mono-exponential modelling was selected from a list to fit the voxelwise time activity curves. The area under the fit curve was then calculated per-voxel, resulting in a time-integrated activity (TIA) image. A 177Lu Voxel S Value dose kernel determined by Lanconelli et al [2] was applied to this TIA image, after which the CT image was used for density correction of the resulting voxelwise dose map. The mean right and left kidney doses were retrieved from this dose map. These were compared to a kidney dose limit of 23 Gy to determine the maximum number of 7.4GBq cycles of therapy that could have been administered, with the assumption that the kidney absorbed dose per cycle has low inter-cycle variability. It is noteworthy that this dose limit was determined from external beam radiation therapy and it is probable that the dose limit for 177Lu-DOTATATE would actually be higher due to a lower dose rate and non-uniform distribution.

Results: For each patient investigated, the number of treatment cycles could have been increased (from the standard of 4) before reaching the assumed 23 Gy maximum tolerated limit to kidney. The maximum numbers of cycles were found to be 7, 8, and 11, such that the cumulative activity administered over the course of treatment could have been increased from 29.6GBq in a standard 4-cycle regimen to an average of 64.1GBq while keeping kidney absorbed dose within tolerance limits. Assuming low inter-cycle variability in dose distribution, this additional activity would have increased the cumulative tumor absorbed dose by an average of about 117%. Discussion: A patient-specific dosimetry method for 177Lu-DOTATATE and its potential use in guiding treatment regimens was demonstrated. In each of the 3 patients assessed, a substantially larger cumulative activity could have been administered while remaining within kidney absorbed dose tolerance, increasing the cumulative absorbed tumor dose. This increased tumor dose may increase the potential for treatment efficacy and positive patient outcomes. References: [1]M. Sandstrӧm et al., "Individualized Dosimetry of Kidney and Bone Marrow in Patients Undergoing 177Lu-DOTA-Octreotate Treatment", Journal of Nuclear Medicine, vol. 54, no. 1, pp. 33-41, 2013. [2]N. Lanconelli et al., "A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions", Physics in Medicine and Biology, vol. 57, no. 2, pp. 517-533, 2012.