Evaluation of accuracy in simultaneous dual-radionuclide activity quantification in preclinical instruments – scintillation counter, digital autoradiography and micro-SPECT/CT

Introduction: The development and optimization of methods for multi-radionuclide measurements in preclinical in vivo and ex vivo SPECT imaging could potentially improve studies in which more than one pharmaceutical is being investigated. The aim of this study is to quantitatively compare and evaluate different methods for these types of measurements using three different modalities – a small animal SPECT/CT, a scintillation counter and a digital autoradiography instrument. This work will also investigate the possibilities of performing a multi-radionuclide study in practice through an animal pilot study. Materials and methods: Phantom measurements were performed on all three instruments, comparing their ability to quantify activity when a single radionuclide is measured in contrast to when two radionuclides are used. For these purposes, the two radionuclides 99mTTc and 111In were used. For the animal pilot study, the HER2-targeting Affibody and Trastuzumab were labeled with 99mTc and 111In respectively. Ten NMRI mice (male and female) were injected with 99mTTc -Affibody and 111In-trastuzumab and imaged using a small animal SPECT/CT camera. Scintillation counting and digital autoradiography were used to measure and/or image the activity in excised organs. Results: Differences between single and dual-radionuclide measurements was about 5 % for the scintillation counter and the small animal SPECT/CT system. The same holds for the digital autoradiography system, except for low statistics where 99mTc was overestimated. Phantom measurements also suggest that correction factors could be calculated, if more data was acquired. In the animal pilot study, all imaging cameras in the study managed to visualize and quantify both radiotracers using dual-radionuclide protocols. Conclusions: This study has shown the possibility to perform quantitative dual-radionuclide measurements on all systems used in this study. Results from the phantom studies suggest that corrections for instrument dead-time and crosstalk could be made. More data is needed in order to calculate such correction factors accurately following the protocols suggested in this study