Standardized Input Function for 18F-FDG PET Studies in Mice: A Cautionary Study.

Marie Meyer,Paolo Zanotti-Fregonara,Philippe Fernandez,Lucie Le-Bras,Chin-Tu Chen

doi:10.1371/journal.pone.0168667

Abstract

Aim of the StudyThe aim of this study was to assess the accuracy of a standardized arterial input function (SAIF) for positron emission tomography 18F-FDG studies in mice. In particular, we tested whether the same SAIF could be applied to populations of mice whose fasting conditions differed.MethodsThe SAIF was first created from a population of fasting mice (n = 11) and validated within this group using a correlation analysis and a leave-one-out procedure. Then, the SAIF was prospectively applied to a population of non-fasting mice (n = 16). The SAIFs were scaled using a single individual blood sample taken 25 min after injection. The metabolic rates of glucose (CMRglc) calculated with the SAIFs were compared with the reference values obtained by full arterial sampling (AIF).ResultsIn both populations of mice, CMRglc values showed a very small bias but an important variability. The SAIF/AIF CMRglc ratio in the fasting mice was 0.97 ± 0.22 (after excluding a major outlier). The SAIF/AIF CMRglc ratio in the non-fasting mice was 1.04 ± 0.22. This variability was due to the presence of cases in which the SAIF poorly estimated the shape of the input function based on full arterial sampling.ConclusionAlthough SAIF allows the estimation of the 18F-FDG mice input function with negligible bias and independently from the fasting state, errors in individual mice (as high as 30–50%) cause an important variability. Alternative techniques, such as image-derived input function, might be a better option for mice PET studies.

Highlights

Positron Emission Tomography (PET) imaging in rodents is a fundamental step for evaluating new radioligands and for studying the effects of therapeutic agents.Absolute quantification with PET often requires the catheterization of an artery to measure the plasma concentration of the tracer over time, i.e. the arterial input function (AIF)
The standardized arterial input function (SAIF)/AIF cerebral metabolic rate of glucose (CMRglc) ratio in the non-fasting mice was 1.04 ± 0.22. This variability was due to the presence of cases in which the SAIF poorly estimated the shape of the input function based on full arterial sampling
SAIF allows the estimation of the 18F-FDG mice input function with negligible bias and independently from the fasting state, errors in individual mice cause an important variability

Summary

Introduction

Absolute quantification with PET often requires the catheterization of an artery to measure the plasma concentration of the tracer over time, i.e. the arterial input function (AIF) This procedure is challenging in rats [1] and it is basically always avoided in mice, due to the small caliber of their arteries and because only a small volume of blood can be removed without altering physiological functions. The most common approach is to measure the input function directly from the PET images (image-derived input function, IDIF) using the time-activity curve of a blood pool, such as the heart [2,3,4] This technique is sensitive to partial volume effects and noise in the images, it requires a fast PET images acquisition protocol in order to maximize the chances to capture the peak of the arterial input function and, unless a data-driven algorithm is used, it is operator-dependent [5]. As demonstrated by several studies in humans, techniques validated using the physical parameters and acquisition characteristics of a particular scanner may not be transposable to different machines [7, 8]

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