Development and performance test of an online blood sampling system for determination of the arterial input function in rats

BACKGROUND: For positron emission tomography (PET) kinetic modelling, an accurate determination of the arterial input function is required. In this study, a blood sampling system was developed and tested using different radiotracers in rats. METHODS: The detector consists of pairs of lutetium yttrium oxyorthosilicate (LYSO) detectors, photomultiplier tubes and lead shield assembled within a steel casing working in coincidence mode. Rats were cannulated with microtubes in the femoral artery and vein for arterial blood sampling as well as administration of the PET tracers. Connected PTFE microtubes were centred between the LYSO crystals using a special holder. To enhance sensitivity, three layers with two coils were used. A flexible tube pump was used to ensure a constant blood flow. Performance of the detector was assessed with [(18)F]fludeoxyglucose (FDG), [(18)F]ciprofloxacin, (R)-[(11)C]verapamil, [(11)C]tariquidar, [(11)C]mephobarbital and [(11)C]MC113. Obtained input function curves were compared with manual samples drawn every 5 s during the first 3 min and further on at 5, 10, 20, 30, 40, 50 and 60 min after radiotracer injection. After manual sampling, an arterio/venous shunt was established. Shape and area-under-the-curve (AUC; Bq/μl*h) of the input functions were evaluated. RESULTS: The developed detector system provided an absolute sensitivity of 6.5%. Maximum peak values agreed well between manual samples and the detector with a mean difference of −0.4% ± 7.0% (max 12.0%, min −9.9%). AUC values also exhibited an excellent correlation (R = 0.996) between manual sampling and detector measurements with a mean difference of 9.3% ± 9.7% (max 24.1%, min −3.2%). The system was able to measure peak blood activity concentration levels of 110 to 2,000 Bq/μl which corresponds to injected activities from 5.5 to 100 MBq depending on the used radiotracer, applied volume and weight of the animal. CONCLUSIONS: This study demonstrates that the developed blood sampling system can be used for in vivo small animal PET studies in rats in a reliable way. The usage of the systems enhances the accuracy of the input curve as handling of small blood samples especially with low activity (as for C-11) is prone to measurement errors. Additionally, the radiation dose of the experimenters can be reduced, as it is not required anymore to continuously draw samples where the personal is in close contact to the radioactive animals and blood.