title: Sensitivity Analysis of a Physiologically Based Pharmacokinetic Model Used for Treatment Planning in Peptide Receptor Radionuclide Therapy.
abstract: The aim of this work was to evaluate the sensitivity of time-integrated activity coefficients (TIACs) on the erroneously chosen prior knowledge in a physiologically based pharmacokinetic (PBPK) model used for treatment planning in peptide receptor radionuclide therapy (PRRT). Parameters of the PBPK model were fitted to the biokinetic data of 15 patients after the injection of (111)In-DTPAOC. The fittings were performed using fixed parameter values taken from literature as prior knowledge (reference case, Ref). The fixed parameters were gender, physical information (e.g., body weight), dissociation rate koff, dissociation constant KD, fraction of blood flow, and spleen and liver volumes. The fittings were repeated with changed fixed parameters (Changed). The relative deviations (RDs) of TIACs calculated from Changed and Ref were analyzed for kidneys, tumor, liver, spleen, remainder, whole body, and serum. A changed koff has the largest effect on RD, the largest RD values were found for changed koff = 0.001 L/min: RDkidneys = (3 ± 3)%, RDtumor = (0.5 ± 4)%, RDliver = (6 ± 9)%, RDspleen = (5 ± 5)%, RDremainder = (2 ± 31)%, RDserum = (-4 ± 25)%, and RDwholebody = (3 ± 16)%. For other changed parameters, the maximum RDs were <1%. The calculation of organ TIACs in PRRT using the PBPK model was little affected by assigning wrong prior knowledge to the evaluated patients. The calculation of bone marrow-absorbed doses could be affected by the inaccurate TIACs of serum and remainder in the case of an inadequate koff.
authors.affiliation: 1 Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University , Mannheim, Germany .|2 Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University , Mannheim, Germany .
authors.forename: Deni
authors.initials: D
authors.lastname: Hardiansyah
authors.affiliation: 1 Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University , Mannheim, Germany .|3 Digitale Signalverarbeitung , Information Technology Faculty, Hochschule Mannheim, Mannheim, Germany .
authors.forename: Nusrat Jihan
authors.initials: NJ
authors.lastname: Begum
authors.affiliation: 4 Department of Nuclear Medicine, University Hospital Ulm , Ulm, Germany .
authors.forename: Peter
authors.initials: P
authors.lastname: Kletting
authors.affiliation: 5 Klinik für Nuklearmedizin, University Hospital, RWTH Aachen University , Aachen, Germany .|6 Department of Nuclear Medicine, Maastricht University Medical Center (MUMC+) , Maastricht, The Netherlands .
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.affiliation: 1 Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University , Mannheim, Germany .
authors.forename: Gerhard
authors.initials: G
authors.lastname: Glatting
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D015282:Octreotide / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D018000:Receptors, Peptide / Q000378:metabolism*
chemical_list: D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; C071632:SDZ 215-811; D004369:Pentetic Acid; D015282:Octreotide
keywords: peptide-receptor radionuclide therapy (PRRT); physiologically-based pharmacokinetic (PBPK) modeling; prior knowledge; time-integrated activity coefficient (TIAC)