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Open Access 01-12-2016 | Original research

Pre-clinical quantitative imaging and mouse-specific dosimetry for ¹¹¹In-labelled radiotracers

Authors: Ana M. Denis-Bacelar, Sarah E. Cronin, Chiara Da Pieve, Rowena L. Paul, Sue A. Eccles, Terence J. Spinks, Carol Box, Adrian Hall, Jane K. Sosabowski, Gabriela Kramer-Marek, Glenn D. Flux

Published in: EJNMMI Research | Issue 1/2016

Abstract

Background

Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare the radiobiological effects of therapeutic agents prior to in-human studies. The aim of this study was to investigate the challenges and feasibility of pre-clinical quantitative imaging and mouse-specific dosimetry of ¹¹¹In-labelled radiotracers.

Attenuation, scatter and partial volume effects were studied using phantom experiments, and an activity calibration curve was obtained for varying sphere sizes. Six SK-OV-3-tumour bearing mice were injected with ¹¹¹In-labelled HER2-targeting monoclonal antibodies (mAbs) (range 5.58–8.52 MBq). Sequential SPECT imaging up to 197 h post-injection was performed using the Albira SPECT/PET/CT pre-clinical scanner. Mice were culled for quantitative analysis of biodistribution studies. The tumour activity, mass and percentage of injected activity per gram of tissue (%IA/g) were calculated at the final scan time point and compared to the values determined from the biodistribution data. Delivered ¹¹¹In-labelled mAbs tumour absorbed doses were calculated using mouse-specific convolution dosimetry, and absorbed doses for ⁹⁰Y-labelled mAbs were extrapolated under the assumptions of equivalent injected activities, biological half-lives and uptake distributions as for ¹¹¹In.

Results

For the sphere sizes investigated (volume 0.03–1.17 ml), the calibration factor varied by a factor of 3.7, whilst for the range of tumour masses in the mice (41–232 mg), the calibration factor changed by a factor of 2.5. Comparisons between the mice imaging and the biodistribution results showed a statistically significant correlation for the tumour activity (r = 0.999, P < 0.0001) and the tumour mass calculations (r = 0.977, P = 0.0008), whilst no correlation was found for the %IA/g (r = 0.521, P = 0.29). Median tumour-absorbed doses per injected activity of 52 cGy/MBq (range 36–69 cGy/MBq) and 649 cGy/MBq (range 441–950 cGy/MBq) were delivered by ¹¹¹In-labelled mAbs and extrapolated for ⁹⁰Y-labelled mAbs, respectively.

Conclusions

This study demonstrates the need for multidisciplinary efforts to standardise imaging and dosimetry protocols in pre-clinical imaging. Accurate image quantification can improve the calculation of the activity, %IA/g and absorbed dose. Diagnostic imaging could be used to estimate the injected activities required for therapeutic studies, potentially reducing the number of animals used.

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Title: Pre-clinical quantitative imaging and mouse-specific dosimetry for 111In-labelled radiotracers
Authors: Ana M. Denis-Bacelar
Sarah E. Cronin
Chiara Da Pieve
Rowena L. Paul
Sue A. Eccles
Terence J. Spinks
Carol Box
Adrian Hall
Jane K. Sosabowski
Gabriela Kramer-Marek
Glenn D. Flux
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2016
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-016-0238-z

At a glance: The STEP trials

Springer Medicine

Pre-clinical quantitative imaging and mouse-specific dosimetry for ¹¹¹In-labelled radiotracers

Abstract

Background

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

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