Quantification of CMRGlc of mice with fully automated arterial blood sampling system

Objectives This study aims at proposing fully automated blood sampling system for kinetic analysis to mice. Quantitative PET imaging requires radioactivity concentrations in both of arterial plasma and whole blood to estimate a behavior of an administered radiopharmaceutical in target organs. A small animal, especially mice, restricts a volume of blood sample to a few micro-liters, and a rapid change in a time activity curve (TAC) requires frequent samplings. We have developed a system for TAC acquisition to mice [1: Kimura Y. Phys Med Biol, 58: 7889-903, 2013.], but the blood sampling was manually conducted. We report the results of fully quantitative measurements of cerebral metabolic rate of glucose (CMRGlc) in mice using the newly developed automated blood sampling system.

Methods The system consists of a syringe pump, solenoid pinch valves, and a catheter kit. The catheter kit has a hydrophilic inner wall to enable smooth blood flow, and is filled with the saline to wash the radioactivity remaining on the inner wall. The blood in the catheter is separated from the saline with a small air layer. PE-8 catheter was inserted into the femoral artery. Immediately after injection of 18F-FDG (13.7 MBq/0.1 mL) to eight wild type male mice, arterial blood samples were drawn using the syringe pump in the system. The blood pressure of mice varies during a PET scan, and the pump makes the sampling reliable. The sampled blood was sent to CD-Well that can measure radioactivity concentration (Bq/μL) using a few micro-liter of blood in the plasma and whole blood separately. Blood samplings were conducted at 10 s × 9, 70 s × 2, 120 s × 1, 250 s × 1, 10 min × 2, and 30 min × 1, 16 samplings in 60 min. Concurrently, dynamic PET scans were conducted using LabPET-8 (TriFoil Imaging Inc.). The full kinetics modeling using two-tissue-three-compartment model was applied to make CMRGlc images where k4 was not assumed zero and blood volume was also estimated.

Results ROIs were defined on the brain regions. Mean CMRGlc were 5.43±1.98 (mg/100g/min) consistent with the previous report [2: Toyama H. J Nucl Med 45: 1398-405, 2004.].

Conclusions The automated micro-liter ordered blood sampling system is useful for kinetic analysis to mice.

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