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

Ann Nucl Med. 2019 Aug;33(8):586-593. doi: 10.1007/s12149-019-01368-3. Epub 2019 May 22.

Abstract

Objective: The 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.

Methods: Under 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 ± 3.93 MBq in 0.1 mL 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 min as follows: 10 s × 9; 70 s × 2; 120 s × 1; 250 s × 1; 10 min × 2; and 30 min × 1. 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.

Results: No significant differences were observed between the manual and ABDS measurements. A proportional error was detected only for plasma. The mean ± standard deviation CMRglc value in the mice was 5.43 ± 1.98 mg/100 g/min (30.2 ± 11 μmol/min/100 g), consistent with a previous report.

Conclusions: The automated microliter-ordered blood sampling system developed in the present study appears to be useful for absolute quantification of CMRglc in mice PET studies.

Keywords: Automated blood sampling system; CD-Well; CMRglc; FDG; Small-animal PET.

MeSH terms

  • Animals
  • Automation
  • Blood Specimen Collection / methods*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Glucose / metabolism
  • Kinetics
  • Male
  • Mice
  • Positron-Emission Tomography / methods*

Substances

  • Glucose