Sensitivity Analysis of a Physiologically Based Pharmacokinetic Model Used for Treatment Planning in Peptide Receptor Radionuclide Therapy

Deni Hardiansyah, Nusrat Jihan Begum, Peter Kletting, Felix M. Mottaghy, Gerhard Glatting*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Web of Science)

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 In-111-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 k(off), dissociation constant K-D, 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 k(off) has the largest effect on RD, the largest RD values were found for changed k(off) = 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
Original languageEnglish
Pages (from-to)217-224
JournalCancer Biotherapy and Radiopharmaceuticals
Volume31
Issue number6
DOIs
Publication statusPublished - Aug 2016

Keywords

  • peptide-receptor radionuclide therapy (PRRT)
  • physiologically-based pharmacokinetic (PBPK) modeling
  • prior knowledge
  • time-integrated activity coefficient (TIAC)

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