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Arterial input function sampling without surgery in rats for positron emission tomography molecular imaging

Croteau, Etienne; Poulin, Eric; Tremblay, Sébastien; Dumulon-Perreault, Véronique; Sarrhini, Otman; Lepage, Martin; Lecomte, Roger

Nuclear Medicine Communications: June 2014 - Volume 35 - Issue 6 - p 666–676
doi: 10.1097/MNM.0000000000000097
Original Articles

Aim: The purpose of this study was to develop a minimally invasive procedure to derive an arterial input function (AIF) in rats through tail artery blood sampling for pharmacokinetic modeling in preclinical PET molecular imaging studies. The procedure involved a microvolumetric blood counter (μBC) and a correction to compensate for delay and dispersion of the automatic blood sampling.

Materials and methods: AIFs were simultaneously obtained from femoral and tail arteries in rats, manually and using a μBC, after 18F-FDG injection (n=6) in order to compare the shape of the AIFs and the kinetic analysis results at equilibrium and after implementation of a dispersion correction method. These AIFs were used to estimate the myocardial metabolic rate of glucose (MMRG). AIFs were also obtained from a single withdrawal site by three methods to confirm accurate MMRG values: manual tail artery (n=5), μBC tail artery (n=5), and μBC femoral artery (n=3).

Results: Simultaneous withdrawal at equilibrium results in similar AIF shapes and influx rate constants (Ki) from Patlak analysis (P>0.05). Manually withdrawn and dispersion-corrected μBC AIFs in the simultaneous experiment did not reveal statistically different shapes and constants (K1, Ki) from a three-compartment kinetic analysis, regardless of the withdrawal methods or sites (P>0.05). Kinetic analysis of the three single-site blood sampling methods yielded similar MMRG (one-way ANOVA; Patlak, P=0.52; three-compartment, P=0.10).

Conclusion: Both minimally invasive manual withdrawal and dispersion-corrected μBC-based blood sampling in the tail artery are reliable methods for deriving AIFs for pharmacokinetic follow-up studies in the same animal.

Department of Nuclear Medicine and Radiobiology, Sherbrooke Molecular Imaging Center, Étienne-Le Bel Clinical Research Center of CHUS, Université de Sherbrooke, Québec, Canada

Correspondence to Etienne Croteau, PhD, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue N., Sherbrooke, Québec, Canada J1H 5N4 Tel: +1 819 346 1110 x11868; fax: +1 819 829 3238; e-mail: etienne.croteau@usherbrooke.ca

Received November 27, 2013

Accepted January 28, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins