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

Biophysics and Medical Imaging Program, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine

Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany

Author to whom correspondence should be addressed.

Academic Editors: Matilde Merino-Sanjuán, Virginia Merino Sanjuán and Victor Mangas Sanjuán

Pharmaceutics 2021, 13(12), 2132; https://doi.org/10.3390/pharmaceutics13122132

Received: 15 October 2021 / Revised: 4 December 2021 / Accepted: 7 December 2021 / Published: 10 December 2021

(This article belongs to the Special Issue Physiologically-Based Pharmacokinetics (PBPK) and Biopharmaceutics (PBBM) Modeling)

View Full-Text Download PDF

Browse Figures

Citation Export

Abstract

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 ²¹²Pb-labeled somatostatin analogs (²¹²Pb-SSTA). The model describes pharmacokinetics of ²¹²Pb-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 ²¹²Po contributes more than 50% to absorbed doses in most tissues. Using this model, it is demonstrated that α-PRRT based on ²¹²Pb-SSTA results in lower absorbed doses in non-target tissue than α-PRRT based on ²¹²Bi-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 ²¹²Pb-SSTA-PBPK model accelerates the translation from bench to bedside by enabling better experimental design and by improving the understanding of the underlying mechanisms. View Full-Text

Keywords: murine PBPK model; neuroendocrine tumors; α-PRRT; in vivo alpha particle generators; [²¹²Pb]Pb-DOTAMTATE

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
ZIP-Document (ZIP, 558 KiB)

Share and Cite

MDPI and ACS Style

Zaid, N.R.R.; Kletting, P.; Winter, G.; Prasad, V.; Beer, A.J.; Glatting, G. A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice. Pharmaceutics 2021, 13, 2132. https://doi.org/10.3390/pharmaceutics13122132

AMA Style

Zaid NRR, Kletting P, Winter G, Prasad V, Beer AJ, Glatting G. A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice. Pharmaceutics. 2021; 13(12):2132. https://doi.org/10.3390/pharmaceutics13122132

Chicago/Turabian Style

Zaid, Nouran R.R., Peter Kletting, Gordon Winter, Vikas Prasad, Ambros J. Beer, and Gerhard Glatting. 2021. "A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice" Pharmaceutics 13, no. 12: 2132. https://doi.org/10.3390/pharmaceutics13122132

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

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

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI