Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET

Abstract

ObjectiveThe objective of the present study was to develop a fully automated blood sampling system for kinetic analysis in mice positron emission tomography (PET) studies. Quantitative PET imaging requires radioactivity concentrations in arterial plasma to estimate the behavior of an administered radiopharmaceutical in target organs. Conventional manual blood sampling has several drawbacks, such as the need for troubleshooting in regard to blood collection, necessary personnel, and the radiation exposure dose. We recently developed and verified the operability of a fully automated blood sampling system (automatic blood dispensing system—ABDS). Here, we report the results of fully quantitative measurements of the cerebral metabolic rate of glucose (CMRglc) in mice using the ABDS.MethodsUnder 1% isoflurane anesthesia, a catheter was inserted into the femoral artery of nine wild-type male mice. Immediately after injection of 18F-fluorodeoxyglucose (FDG) (13.2\u2009±\u20093.93\xa0MBq in 0.1\xa0mL saline), arterial blood samples were drawn using the ABDS and then analyzed using CD-Well, a system we previously developed that can measure radioactivity concentration (Bq/μL) using a few microliters of blood in the plasma and whole blood separately. In total, 16 blood samplings were conducted in 60\xa0min as follows: 10\xa0s\u2009×\u20099; 70\xa0s\u2009×\u20092; 120\xa0s\u2009×\u20091; 250\xa0s\u2009×\u20091; 10\xa0min\u2009×\u20092; and 30\xa0min\u2009×\u20091. Dynamic PET scans were conducted concurrently using a small-animal PET/computed tomography (CT) (PET/CT) scanner. Full kinetics modeling using a two-tissue–three-compartment model was applied to calculate CMRglc. Blood volume was also estimated.ResultsNo significant differences were observed between the manual and ABDS measurements. A proportional error was detected only for plasma. The mean\u2009±\u2009standard deviation CMRglc value in the mice was 5.43\u2009±\u20091.98\xa0mg/100\xa0g/min (30.2\u2009±\u200911 μmol/min/100\xa0g), consistent with a previous report.ConclusionsThe automated microliter-ordered blood sampling system developed in the present study appears to be useful for absolute quantification of CMRglc in mice PET studies.