The feasibility of performing longitudinal measurements in mice using small animal PET imaging and a microfluidic blood sampling device

To minimize blood loss in a mouse during quantitative PET imaging, we developed an automated blood sampling device using microfluidic technology. The integrated technology was proven reliable in measuring the cerebral glucose metabolism. In this study, we validated the performance of the microfluidic device using in vivo mouse studies. We examined the stability of the mouse in sequential PET scans to access the feasibility of acquiring multiple measurements from the same mouse over time. Cardiac output and body temperature were chosen as physiological indicators of mouse stability. Three control and three tumor-bearing mice were studied. Sixty minutes of PET data were acquired for each mouse following a bolus injection of 3´-deoxy-3´-[F- 18]fluorothymidine (FLT; ~250 muCi). 18 serial blood samples, 0.25 mul each, were taken from the femoral artery using the microfluidic device. Body temperatures were monitored before and after the scan. Immediately following the FLT scan, a 40-minute quantitative FDG (~300 muCi) PET scan was performed on the tumor-bearing mouse. Using a previously described first-pass angiographic method, we calculated two cardiac outputs for each mouse using the first 15-second data of the FLT and FDG scans respectively. The FLT data showed that the image-derived blood curve correlated (R squares > 0.95) well with the blood curve derived from the 18 arterial blood samples. The body temperatures (mean: 32.1degC) of the animal varied < 1% after the FLT studies. The cardiac outputs of the three tumor- bearing mice before the 18 blood samples were taken were 19.2, 15.7, 18.3 and were 18.7, 16.3, 18.9 ml/min afterward (i.e. < 4% change). We validated the performance of the microfluidic device using in vivo FLT-PET imaging. The physiology of the animal remained stable after the imaging and blood sampling procedure. Reliable longitudinal measurements using PET imaging are expected to be feasible with a protected arterial catheter.