skip to main content
Language:
Search Limited to: Search Limited to: Resource type Show Results with: Show Results with: Search type Index

A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice

Pharmaceutics, 2021-12, Vol.13 (12), p.2132 [Peer Reviewed Journal]

2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2021 by the authors. 2021 ;ISSN: 1999-4923 ;EISSN: 1999-4923 ;DOI: 10.3390/pharmaceutics13122132 ;PMID: 34959413

Full text available

Citations Cited by
  • Title:
    A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice
  • Author: Zaid, Nouran R R ; Kletting, Peter ; Winter, Gordon ; Prasad, Vikas ; Beer, Ambros J ; Glatting, Gerhard
  • Subjects: [212Pb]Pb-DOTAMTATE ; Binding sites ; Biodistribution ; Dosimetry ; Generators ; in vivo alpha particle generators ; Kidneys ; murine PBPK model ; Neuroendocrine tumors ; Peptides ; Pharmacokinetics ; Proteins ; Software utilities ; α-PRRT
  • Is Part Of: Pharmaceutics, 2021-12, Vol.13 (12), p.2132
  • Description: In vivo alpha particle generators have great potential for the treatment of neuroendocrine tumors in alpha-emitter-based peptide receptor radionuclide therapy (α-PRRT). Quantitative pharmacokinetic analyses of the in vivo alpha particle generator and its radioactive decay products are required to address concerns about the efficacy and safety of α-PRRT. A murine whole-body physiologically based pharmacokinetic (PBPK) model was developed for Pb-labeled somatostatin analogs ( Pb-SSTA). The model describes pharmacokinetics of Pb-SSTA and its decay products, including specific and non-specific glomerular and tubular uptake. Absorbed dose coefficients (ADC) were calculated for bound and unbound radiolabeled SSTA and its decay products. Kidneys received the highest ADC (134 Gy/MBq) among non-target tissues. The alpha-emitting Po contributes more than 50% to absorbed doses in most tissues. Using this model, it is demonstrated that α-PRRT based on Pb-SSTA results in lower absorbed doses in non-target tissue than α-PRRT based on Bi-SSTA for a given kidneys absorbed dose. In both approaches, the energies released in the glomeruli and proximal tubules account for 54% and 46%, respectively, of the total energy absorbed in kidneys. The Pb-SSTA-PBPK model accelerates the translation from bench to bedside by enabling better experimental design and by improving the understanding of the underlying mechanisms.
  • Publisher: Switzerland: MDPI AG
  • Language: English
  • Identifier: ISSN: 1999-4923
    EISSN: 1999-4923
    DOI: 10.3390/pharmaceutics13122132
    PMID: 34959413
  • Source: Geneva Foundation Free Medical Journals at publisher websites
    PubMed Central
    ROAD: Directory of Open Access Scholarly Resources
    ProQuest Central
    DOAJ Directory of Open Access Journals
Back to results list
INSPIRE LIBRARY - TON DUC THANG UNIVERSITY (84-028) 37 755 057 Feedback
19 Nguyen Huu Tho St. Dist.7, HCM thuvien@tdtu.edu.vn

Copyright © 2017 INSPIRE LIBRARY - TON DUC THANG UNIVERSITY

Searching Remote Databases, Please Wait