Preclinical dosimetry models and the prediction of clinical doses of novel positron emission tomography radiotracers

Dosimetry models using preclinical positron emission tomography (PET) data are commonly employed to predict the clinical radiological safety of novel radiotracers. However, unbiased clinical safety profiling remains difficult during the translational exercise from preclinical research to first-in-hu...

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Bibliographic Details
Published in:	Scientific reports Vol. 10; no. 1; p. 15985
Main Authors:	Garrow, Adam A., Andrews, Jack P. M., Gonzalez, Zaniah N., Corral, Carlos A., Portal, Christophe, Morgan, Timaeus E. F., Walton, Tashfeen, Wilson, Ian, Newby, David E., Lucatelli, Christophe, Tavares, Adriana A. S.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 29-09-2020
Subjects:	631/1647 631/337 Administration, Intravenous Animals Bias Female Fluorine Radioisotopes - administration & dosage Fluorodeoxyglucose F18 - administration & dosage Humanities and Social Sciences Humans Male Models, Animal multidisciplinary Positron-Emission Tomography - methods Radiometry Rats Science Science (multidisciplinary) Whole Body Imaging - methods
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Summary:	Dosimetry models using preclinical positron emission tomography (PET) data are commonly employed to predict the clinical radiological safety of novel radiotracers. However, unbiased clinical safety profiling remains difficult during the translational exercise from preclinical research to first-in-human studies for novel PET radiotracers. In this study, we assessed PET dosimetry data of six 18 F-labelled radiotracers using preclinical dosimetry models, different reconstruction methods and quantified the biases of these predictions relative to measured clinical doses to ease translation of new PET radiotracers to first-in-human studies. Whole-body PET images were taken from rats over 240 min after intravenous radiotracer bolus injection. Four existing and two novel PET radiotracers were investigated: [ 18 F]FDG, [ 18 F]AlF-NOTA-RGDfK, [ 18 F]AlF-NOTA-octreotide ([ 18 F]AlF-NOTA-OC), [ 18 F]AlF-NOTA-NOC, [ 18 F]ENC2015 and [ 18 F]ENC2018. Filtered-back projection (FBP) and iterative methods were used for reconstruction of PET data. Predicted and true clinical absorbed doses for [ 18 F]FDG and [ 18 F]AlF-NOTA-OC were then used to quantify bias of preclinical model predictions versus clinical measurements. Our results show that most dosimetry models were biased in their predicted clinical dosimetry compared to empirical values. Therefore, normalization of rat:human organ sizes and correction for reconstruction method biases are required to achieve higher precision of dosimetry estimates.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-020-72830-w