title: Dependence of treatment planning accuracy in peptide receptor radionuclide therapy on the sampling schedule.
abstract: BACKGROUND
  Peptide 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 (111)In-labeled-diethylenetriaminopentaacetic acid-octreotide (DTPAOC; Octreoscan™).
  
  
  METHODS
  Pre-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.
  
  
  RESULTS
  When 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.
  
  
  CONCLUSIONS
  When 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.
authors.affiliation: Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Maaß
authors.affiliation: Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Jan Philipp
authors.initials: JP
authors.lastname: Sachs
authors.affiliation: Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Deni
authors.initials: D
authors.lastname: Hardiansyah
authors.affiliation: Klinik für Nuklearmedizin, University Hospital, RWTH Aachen University, Aachen, Germany.|Department of Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: Department of Nuclear Medicine, Ulm University, Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kletting
authors.affiliation: Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. gerhard.glatting@medma.uni-heidelberg.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Glatting
keywords: Neuroendocrine tumor (NET); Optimal sampling schedule; Peptide receptor radionuclide therapy (PRRT); Physiologically based pharmacokinetic (PBPK) modeling; Time-integrated activity coefficient (TIAC)