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

ABSTRACT: 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 ¹⁸F-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: [¹⁸F]FDG, [¹⁸F]AlF-NOTA-RGDfK, [¹⁸F]AlF-NOTA-octreotide ([¹⁸F]AlF-NOTA-OC), [¹⁸F]AlF-NOTA-NOC, [¹⁸F]ENC2015 and [¹⁸F]ENC2018. Filtered-back projection (FBP) and iterative methods were used for reconstruction of PET data. Predicted and true clinical absorbed doses for [¹⁸F]FDG and [¹⁸F]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.

SUBMITTER: Garrow AA

PROVIDER: S-EPMC7525662 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Garrow Adam A AA Andrews Jack P M JPM Gonzalez Zaniah N ZN Corral Carlos A CA Portal Christophe C Morgan Timaeus E F TEF Walton Tashfeen T Wilson Ian I Newby David E DE Lucatelli Christophe C Tavares Adriana A S AAS

Scientific reports 20200929 1

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 <sup>18</sup>F-labelled radiotracers using preclinical dosimetry models, different reconstruction methods a ...[more]

PMID: 32994530

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

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

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