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

摘要

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~(111)In-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~(111)In-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~(111)In-labelled mAbs tumour?absorbed doses were calculated using mouse-specific convolution dosimetry, and absorbed doses for~(90)Y-labelled mAbs were extrapolated under the assumptions of equivalent injected activities, biological half-lives and uptake distributions as for~(111)In. 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 ?