{"id":2919,"date":"2022-01-19T15:05:40","date_gmt":"2022-01-19T14:05:40","guid":{"rendered":"http:\/\/www.m2olie.de\/?post_type=publications&p=2919"},"modified":"2022-01-19T15:05:40","modified_gmt":"2022-01-19T14:05:40","slug":"a-physiologically-based-pharmacokinetic-model-for-in-vivo-alpha-particle-generators-targeting-neuroendocrine-tumors-in-mice","status":"publish","type":"publications","link":"https:\/\/www.m2olie.de\/en\/publications\/a-physiologically-based-pharmacokinetic-model-for-in-vivo-alpha-particle-generators-targeting-neuroendocrine-tumors-in-mice\/","title":{"rendered":"A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice"},"content":{"rendered":"\n

by Nouran R. R. Zaid<\/a> 1,2,*<\/sup><\/a>, Peter Kletting<\/a> 1,3<\/sup>, Gordon Winter<\/a> 3<\/sup><\/a>, Vikas Prasad<\/a> 3<\/sup>, Ambros J. Beer<\/a> 3<\/sup> and Gerhard Glatting<\/a> 1,3<\/sup><\/p>\n\n\n\n

<\/a>1<\/sup> Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany
2<\/sup> Biophysics and Medical Imaging Program, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
3<\/sup> Department of Nuclear Medicine, Ulm University, 89081 Ulm, Germany
*<\/sup> Author to whom correspondence should be addressed. <\/p>\n\n\n\n

Academic Editors: Matilde Merino-Sanju\u00e1n, Virginia Merino Sanju\u00e1n and Victor Mangas Sanju\u00e1n <\/p>\n\n\n\n

Pharmaceutics<\/em> 2021<\/strong>, 13<\/em>(12), 2132; https:\/\/doi.org\/10.3390\/pharmaceutics13122132<\/a>
Received: 15 October 2021 \/ Revised: 4 December 2021 \/ Accepted: 7 December 2021 \/ Published: 10 December 2021<\/p>\n\n\n\n

(This article belongs to the Special Issue Physiologically-Based Pharmacokinetics (PBPK) and Biopharmaceutics (PBBM) Modeling<\/a>)<\/p>\n\n\n\n

Abstract<\/h2>\n\n\n\n

In vivo alpha particle generators have great potential for the treatment of neuroendocrine tumors in alpha-emitter-based peptide receptor radionuclide therapy (\u03b1-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 \u03b1-PRRT. A murine whole-body physiologically based pharmacokinetic (PBPK) model was developed for 212<\/sup>Pb-labeled somatostatin analogs (212<\/sup>Pb-SSTA). The model describes pharmacokinetics of 212<\/sup>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 212<\/sup>Po contributes more than 50% to absorbed doses in most tissues. Using this model, it is demonstrated that \u03b1-PRRT based on 212<\/sup>Pb-SSTA results in lower absorbed doses in non-target tissue than \u03b1-PRRT based on 212<\/sup>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 212<\/sup>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. View Full-Text<\/a>
<\/p>\n\n\n\n

Keywords: <\/em>murine PBPK model<\/a>; neuroendocrine tumors<\/a>; \u03b1-PRRT<\/a>; in vivo alpha particle generators<\/a>; [212<\/sup>Pb]Pb-DOTAMTATE<\/a><\/p>\n","protected":false},"featured_media":0,"comment_status":"open","ping_status":"closed","template":"","meta":{"footnotes":""},"categories":[],"class_list":["post-2919","publications","type-publications","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/2919","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications"}],"about":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/types\/publications"}],"replies":[{"embeddable":true,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/comments?post=2919"}],"version-history":[{"count":2,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/2919\/revisions"}],"predecessor-version":[{"id":2923,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/2919\/revisions\/2923"}],"wp:attachment":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/media?parent=2919"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/categories?post=2919"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}