Physiologically based pharmacokinetic modeling of 18F-SiFAlin-Asp3-PEG1-TATE in AR42J tumor bearing mice

• Verfasst von: Maaß, Christian [VerfasserIn]
• Verfasst von: Attarwala, Ali Asgar [VerfasserIn]
• Verfasst von: Litau, Shanna [VerfasserIn]
• Verfasst von: Wängler, Carmen [VerfasserIn]
• Verfasst von: Wängler, Björn [VerfasserIn]
• Verfasst von: Glatting, Gerhard [VerfasserIn]
• Titel: Physiologically based pharmacokinetic modeling of 18F-SiFAlin-Asp3-PEG1-TATE in AR42J tumor bearing mice
• Verf.angabe: Christian Maaß, Jose Ricardo Avelar Rivas, Ali Asgar Attarwala, Deni Hardiansyah, Sabrina Niedermoser, Shanna Litau, Carmen Wängler, Björn Wängler, Gerhard Glatting
• E-Jahr: 2016
• Jahr: April 2016
• Umfang: 4 S.
• Fussnoten: Gesehen am 11.04.2019 ; Im Titel ist "18" hochgestellt, "3" und "1" sind tiefgestellt
• Titel Quelle: Enthalten in: Nuclear medicine and biology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1993
• Jahr Quelle: 2016
• Band/Heft Quelle: 43(2016), 4, Seite 243-246
• ISSN Quelle: 1872-9614
• DOI: doi:10.1016/j.nucmedbio.2016.01.001
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Mice
• Sach-SW: Neuroendocrine tumor (NET)
• Sach-SW: Peptide receptor radionuclide therapy (PRRT)
• Sach-SW: Physiologically based pharmacokinetic (PBPK) modeling
• K10plus-PPN: 166315385X

Abstract

Purpose - Peptide receptor radionuclide therapy (PRRT) is commonly performed in the treatment of neuroendocrine tumors (NET), where somatostatin analogs (DOTATATE) are radiolabeled with 90Y, 68Ga or 111In for pre-therapeutic and therapeutic purposes. Quantitative evaluation of the biokinetic data can be performed by using physiologically based pharmacokinetic (PBPK) models. Knowledge about the biodistribution in a pre-clinical setting would allow optimizing the translation from bench to bedside. The aim of this study was to develop a PBPK model to describe the biodistribution of a novel sst2-targeting radiotracer. - Methods - Biokinetic data of six mice after injection of 18F-SiFAlin-Asp3-PEG1-TATE were investigated using two PBPK models. The PBPK models describe the biodistribution of the tracer in the tumor, kidneys, liver, remainder and whole body via blood flow to these organs via absorption, distribution, metabolism and excretion. A recently published sst2 PBPK model for humans (model 1) was used to describe the data. Physiological information in this model was adapted to that of a mouse. Model 1 was further modified by implementing receptor-mediated endocytosis (model 2). Model parameters were fitted to the biokinetic data of each mouse. Model selection was performed by calculating Akaike weights wi using the corrected Akaike Information Criterion (AICc). - Results - The implementation of receptor-mediated endocytosis considerably improved the description of the biodistribution (Akaike weights w1=0% and w2=100% for model 1 and 2, respectively). The resulting time-integrated activity coefficients determined by model 2 were for tumor (0.05±0.02) h, kidneys (0.11±0.01) h and liver (0.02±0.01) h. - Conclusion - Simply downscaling a human PBPK model does not allow for an accurate description of 18F-SiFAlin-Asp3-PEG1-TATE in mice. Biokinetics of this tracer can be accurately and adequately described using a physiologically based pharmacokinetic model including receptor-mediated endocytosis. Thus, an optimized translation from bench to bedside is possible.