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Optimizing Experimental Protocols for Quantitative Behavioral Imaging with ¹⁸F-FDG in Rodents

¹ Medical Department, Brookhaven National Laboratory, Upton, New York, New York; and ² Department of Molecular Pharmacology, Stony Brook University, Stony Brook, New York

Correspondence: For correspondence or reprints contact: Wynne K. Schiffer, PhD, Chemistry Department, Building 555, Brookhaven National Laboratory, Upton, NY 11973. E-mail: wynne{at}bnl.gov

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.

Key Words: glucose metabolic rate • brain imaging • PET • behavior

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