A new tool for molecular imaging:: The microvolumetric β blood counter

Radiotracer kinetic modeling in small animals with PET allows absolute quantification of physiologic and biochemical processes in vivo. It requires blood and tissue tracer concentrations as a function of time. Manual sampling, the reference method for blood tracer concentration measurements, requires fairly large amounts of blood besides being technically difficult and time-consuming. An automated microvolumetric beta blood counter (mu BC) was designed to circumvent these limitations by measuring the blood activity in real time with PET scanning. Methods: The mu BC uses direct beta-particle detection to reduce its footprint and is entirely remote controlled for sampling protocol selection and real-time monitoring of measured parameters. Sensitivity has been determined for the most popular PET radioisotopes (F-18, N-13, C-11, Cu-64). Dispersion within the sampling catheter has been modeled to enable automatic correction. Blood curves obtained with the mu BC were compared with manual samples and PET-derived data. The mu BC was used to estimate the myocardial blood flow (MBF) of mice injected with N-13-ammonia and to compare the myocardial metabolic rate of glucose (MMRG) of rats injected with F-18-FDG for arterial and venous cannulation sites. Results: The sensitivity limit ranges from 3 to 104 Bq/mu L, depending on the isotope and the catheter used, and was found to be adequate for most small-animal studies. Automatic dispersion correction appears to be a good approximation of dispersion-free reference curves. Blood curves sampled with the mu BC are well correlated with curves obtained from manual samples an PET images. With correction for dispersion, the MBF of anesthetized mice at rest was found to be 4.84 +/- 0.5 mL/g/min, which is comparable to values found in the literature for rats. MMRG values derived from the venous blood tracer concentration are underestimated by 60% as compared with those derived from arterial blood. Conclusion: The mu BC is a compact automated counter allowing real-time measurement of blood radioactivity for pharmacokinetic studies in animals as small as mice. Reliable and reproducible, the device makes it possible to increase the throughput of pharmacokinetic studies with reduced blood sample handling and staff exposure, contributing to speed up new drug development and evaluation.