Towards a reproducible protocol for repetitive and semi-quantitative rat brain imaging with (18) F-FDG: exemplified in a memantine pharmacological challenge

Neuroimage. 2014 Aug 1:96:276-87. doi: 10.1016/j.neuroimage.2014.04.004. Epub 2014 Apr 13.

Abstract

The standard uptake value (SUV), commonly used to quantify (18)F-FluoroDeoxyGlucose (FDG) uptake in small animal brain PET imaging, is affected by many factors. In this study the influence of fasting times, inter-scan duration and repetitive scanning on the variability of different SUV measures is investigated. Additionally it is demonstrated that these variables could adversely influence the outcome of a pharmacological challenge when not accounted for. Naive Sprague-Dawley rats (n=20) were randomly divided into five different fasting groups (no fasting up to 24h of fasting). SUV brain uptake values were reproducible in naive animals when a fasting period of at least 12h is used and for shorter fasting periods SUV values need to be corrected for the glucose level. Additionally, a separate animal group (n=6) was sufficiently fasted for 16h and in a longitudinal setting being scanned six times in three weeks. Especially with short inter-scan durations, increasing glucose levels were found over time which was attributed to increased stress due to repeated food deprivation, altered food intake or scan manipulations. As a result, even with controlled and sufficient fasting, blood glucose levels should be taken into account for data quantification. Strikingly, even the brain activation effects of an NMDA-antagonist challenge with memantine could not be detected in experiments with a short inter-scan duration if glucose levels were not taken into account. Correcting for glucose levels decreases the inter- and intra-animal variability for rat brain imaging. SUV corrected for glucose levels yields the lowest inter-animal variation. However, if the body weight changes significantly, as in a long experiment, quantification based on the glucose corrected percentage injected dose (and not SUV) is recommendable as this yields the lowest intra-animal variation.

Keywords: (18) F-FDG; Brain; Glucose; PET; Rat; SUV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Brain / metabolism*
  • Computer Simulation
  • Fasting / physiology*
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Image Enhancement / methods
  • Male
  • Memantine / pharmacology*
  • Metabolic Clearance Rate / drug effects
  • Models, Biological
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Memantine