Natural brain casts of merycoidodonts

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1931
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Abstract
1570

Aim:

Bismuth (213/212Bi) -labeled pharmaceuticals have been effective in targeted alpha particle therapy (TAT). The 45.6- and 60.6-min half-lives of these radionuclides allow for the redistribution of free 213/212Bi throughout the whole body. A challenge in TAT is estimating the contribution of free 213/212Bi to the overall absorbed doses in non-target tissues. Physiologically-based pharmacokinetic (PBPK) modeling can help to overcome this limitation. Therefore, a whole-body 212Bi-PBPK model was developed to describe the pharmacokinetics (PK) of 212Bi in rats.

Methods:

The rat 212Bi-PBPK model was developed and implemented using the modeling software SAAM II version 2.3 (The Epsilon Group, TEG, USA). The model includes main physiological mechanisms, such as blood flow, transcapillary transport and urinary excretion based on parameter values from the literature. 212Bi interactions with red blood cells (RBC), high molecular weight plasma protein (HWPP) and intracellular biological thiols are described. Important PK parameters were estimated using non-decay corrected percentage of injected dose per gram (%ID/g) data for 212Bi in different tissues of unanesthetized rats with an injected activity 2.4 µCi (0.7 fmol) of 212Bi [1]. The corresponding absorbed dose coefficients (ADC) in tissues were calculated.

Results:

Model implementation was successful, and the fitted curves were good according to visual inspection and R2>0.92. The association rates of 212Bi with RBC and HWPP were (0.006 ± 0.003) min-1 and (0.18 ± 0.04) min-1, respectively. The dissociation rates of RBC- and HWPP-bound 212Bi were (0.02 ± 0.01) min-1 and (0.10 ± 0.02) min-1, respectively. 212Bi uptake rates by liver, bone, small intestine, bone marrow and muscle were (0.86 ± 0.13), (3.80 ± 0.65), (0.27 ± 0.05), (1.43 ± 0.29) and (0.007 ± 0.007) min-1 with corresponding ADCs of 0.8, 0.3, 0.3, 0.5 and 0.03 mGy/kBq, respectively. Kidneys had the highest ADC of 6.5 mGy/kBq.

Conclusions:

Kidneys are the dose-limiting organs in 212/213Bi-based TAT. It has been demonstrated that the 212Bi-PBPK model is an effective tool to study 212Bi biodistribution in murine models. Integrating the 212Bi-PBPK model into other murine and human PBPK models of alpha generators can help to further analyze and improve the efficacy and safety of TAT. 1. Hursh JB, Brown C. Tissue Distribution of 212Bi in Rats. Proceedings of the Society for Experimental Biology and Medicine. 1969;131(1):116-120.
Reference Key
openalex_W2334616209 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors M. R. Thorpe
Journal american journal of science
Year 1931
DOI
10.2475/ajs.s5-21.123.193
URL
https://doi.org/10.2475/ajs.s5-21.123.193
Keywords Keywords not found

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