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

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...

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Published in:EJNMMI research 2016-11, Vol.6 (1), p.1
Main Authors: Denis-bacelar, Ana M, Cronin, Sarah E, Da Pieve, Chiara, Paul, Rowena L, Eccles, Sue A, Spinks, Terence J, Box, Carol, Hall, Adrian, Sosabowski, Jane K, Kramer-marek, Gabriela, Flux, Glenn D
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Language:English
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Summary: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
ISSN:2191-219X
DOI:10.1186/s13550-016-0238-z