Dependence of treatment planning accuracy in peptide receptor radionuclide therapy on the sampling schedule

Abstract

BackgroundPeptide receptor radionuclide therapy (PRRT) plays an important role in the treatment of neuroendocrine tumors (NET). Pre-therapeutic dosimetry using the area under the measured time-activity curve (AUC) is important. The sampling schedule for this dosimetry determines the accuracy and reliability of the obtained AUC.The aim of this study was to investigate the effect of reduced number of measurement points (i.e., gamma camera image acquisition or serum measurements) on treatment planning accuracy in PRRT using 111In-labeled-diethylenetriaminopentaacetic acid-octreotide (DTPAOC; Octreoscan™).MethodsPre-therapeutic biokinetic data of 15 NET patients were investigated using a recently developed physiologically based pharmacokinetic (PBPK) model. Two parameter sets were determined (standard or iterative approach) and used for calculation of time-integrated activity coefficients (TIACs) for the tumor, kidneys, liver, spleen, serum, and whole body. TIACs obtained using the full data sets were used as reference. To evaluate the effect of sampling on individual treatment planning, reduced sampling schedules were generated omitting either 1, 2, 3, or 4 organ and serum measurements or all serum measurements for each patient. Relative deviations (RDs) between these and reference TIACs were calculated and used as criterion for treatment planning accuracy. An RD < 0.1 was considered acceptable.ResultsWhen omitting serum measurements, TIAC accuracy remained acceptable (RD < 0.1) for the standard approach. The kidney TIACs could be estimated for both approaches with acceptable RDs using two time points (t = 4 h; 2 d); tumor RDs were <0.3. The iterative approach reduced the range of RD, but did not further reduce the number of needed measurement points (i.e., to achieve an RD <0.1). For both approaches RDs for liver, spleen and whole body were larger than 0.1. However, in the clinical setting these RDs are less relevant as liver and spleen are not organs at risk due to the low absorbed doses.ConclusionsWhen using a priori information of a PBPK model structure combined with Bayesian information about PBPK model parameter distribution, the administered activity could be determined with acceptable accuracy using only two time points (4 h, 2 d) and thus allow a considerable reduction of needed data for individual dosimetry.

The Relevance of Dosimetry in Precision Medicine

“…Two recent publications suggested reducing the number of scans needed for dosimetry. Maaß et al (40) looked into whether the accuracy of treatment planning in PRRT is dependent on the NOTEWORTHY n Improvements in quantification of SPECT/CT images reduce uncertainties in absorbed dose calculations. n There are still limitations concerning bone marrow dosimetry and dosimetry for therapies with a-emitters.…”

Dosimetry methods and clinical applications in peptide receptor radionuclide therapy for neuroendocrine tumours: a literature review

“…Recent research has focussed on optimising the number of time points, for example by only using one late time point [ 74 ]. Maaβ et al applied pharmacokinetic models based on individual and population information to estimate kidney and tumour uptake with different sampling schedules [ 75 ]. For the kidneys, the use of only the 4 h and 2 days time point allowed for sufficient time-integrated activities estimates.…”

“…4 . Sequential imaging is essential to create a proper time-activity curve and determine the cumulative activity in a volume of interest [ 75 , 88 ]. We recommend to use three late time points, with the latest time point at least later than two effective half-lives of the radiopharmaceutical, to accurately fit the tail of the time-activity curve [ 30 ].…”

Technical Note: Optimal sampling schedules for kidney dosimetry based on the hybrid planar/SPECT method in 177Lu‐PSMA therapy

“…In these studies, the dosimetry based on the full time‐activity data set was used as ground truth and compared with minimized data sets. Whether the underlying time‐activity data were measured under optimal conditions, that is, time points, is unclear and has never been investigated . Furthermore, the uncertainty using the full time‐activity data set to the “true” time‐activity curve (TAC) of the investigated patients has never been quantified.…”

“…is unclear and has never been investigated. 8 Furthermore, the uncertainty using the full time-activity data set to the "true" time-activity curve (TAC) of the investigated patients has never been quantified.…”