Abstract
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Objectives: The continuously infused microfluidic radioassay (CIMR) is an in suit detection technique for measuring the dynamic cellular uptake of radiotracers without altering the cellular growth environment. It is a useful tool for investigating the cellular pharmacokinetics and physiology. Also, it is useful for assessing the properties of radiopharmaceuticals. The existing CIMR system with a positron camera can only measure the dynamics of one sample at a time due to the limited imaging field of view (FOV) of the positron camera. To increase the detection throughput, we developed a new CIMR system with a minimized panel PET. With this system, dynamics of parallel or comparison samples can be imaged all at the same time.
Methods: The panel PET-based CIMR detection system contains a microfluidic chip (VI0.4, ibidi GmbH), a peristaltic pump (BT100F, Lead Fluid Technology Co. Ltd.), and an in-house built LYSO-SiPM dual-panel PET. The microfluidic chip has six parallel microchambers; each microchamber has an input port and an output port with female Luer fittings. The peristaltic pump has multiple tubing cassettes and allows transporting of parallel fluids to the parallel microchambers with the same speed. The LYSO-SiPM dual-panel PET has two parallel detection panels. Each panel has four sets of LYSO-SiPM detectors, the dimension of the panel is 5 cm × 5 cm. An imaging stage is placed between the two panels. For the validation of the system, four microchambers without cells are infused with [18F]FDG solution (1-5 MBq/ml), the image of the microfluidic chip is measured simultaneously for 60 min. For the cellular experiment, MDA-MB-231 (human breast adenocarcinoma, 2e4 per microchamber) is inoculated into three of the middle microchambers of the microfluidic chip, leaving one microchamber without cells (as a control chamber to supply the real-time input of the infused radioactive fluids). During the measurement, the [18F]FDG solution (1-5 MBq/ml) is transported with constant low speed (75 μl/min) over the parallel microchambers, and the image is recorded by the panel PET in real-time with a dynamic acquisition mode for 60 min. To count the cell number, the microchannels with cells are imaged by microscopy just before and after the CIMR measurement. After measurement, the image of microchambers is segmented. The averaged counts per voxel of the segmented area are calculated along the time. The kinetic curves are further normalized by the cell numbers. Results: The blank experiment is performed to check whether the four microchambers perform the same way. The dynamic curves of the four microchambers have a similar profile. For the cellular experiment, the parallel samples have similar dynamic uptake profile. With the validation of the blank experiment, the dynamic curve of the blank sample can be set as the dynamic input of the radiotracer medium. Thus, the dynamic uptake curves of the cells are derived by subtraction of the blank curve from the curves of the cellular chambers.
Conclusions: A panel PET-based CIMR system is established. The system allowed simultaneous measurement of the dynamics of multiple samples. With this system, the pharmacokinetics of parallel or comparison samples can be imaged and compared directly. [1] Liu et al. JNM 2016 [2] Xi et al. J Med Imaging 2017 This work was supported by the National Natural Science Foundation of China (No. 81801860), National Key Technology Research and Development Program of the Ministry of Science and Technology of China (No. 2015BAI01B09)