Optimizing experimental protocols for quantitative behavioral imaging with¹⁸F-FDG in rodents

Small-animal PET provides the opportunity to image brain activation during behavioral tasks in animal models of human conditions. The present studies aimed to simplify behavioral imaging procedures without a loss of quantitation by using an intraperitoneal route of administration (no cannulation, no anesthesia) and using a standardized uptake value (SUV) to reduce scan duration. Methods: Sixteen animals with carotid artery cannulations were studied with ¹⁸F-FDG small-animal PET accompanied by serial arterial blood sampling. Ten of these animals were anesthetized and were inside the tomograph during ¹⁸F-FDG uptake, whereas 6 animals were awake in their home cages and scanned after 60 min of uptake. Of the 10 anesthetized animals, 6 received intraperitoneal ¹⁸F-FDG, whereas 4 received intravenous ¹⁸F-FDG, and all 6 awake animals received intraperitoneal ¹⁸F-FDG. Intravenously injected animals were positioned far enough inside the tomograph to obtain region-of-interest-based measures from the heart and the brain. In all animals, a full arterial input function and plasma glucose levels were obtained. To establish the optimal time during ¹⁸F-FDG uptake for blood sampling when using an SUV, a Patlak kinetic model was used to derive absolute rates of glucose metabolism and compared with SUVs calculated using different plasma points from the arterial input function. Results: A single plasma point taken at 60 min after injection for intraperitoneal injections or 45 min after injection for intravenous injections provides a sensitive index of glucose metabolic rate with the highest correlation with data obtained from a fully quantitative input function. Conclusion: These studies support an experimental protocol in which animals can receive the ¹⁸F-FDG tracer injection intraperitoneally, away from the small-animal tomograph and with minimal impact on behavior. Further, animals can occupy the tomograph bed for a 10- to 30-min scan with a consequent increase in animal throughput.