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

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.
AuthorsSteven Deleye, Jeroen Verhaeghe, Leonie wyffels, Stefanie Dedeurwaerdere, Sigrid Stroobants, Steven Staelens
JournalNeuroImage (Neuroimage) Vol. 96 Pg. 276-87 (Aug 01 2014) ISSN: 1095-9572 [Electronic] United States
PMID24736171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Memantine
Topics
  • Animals
  • Brain (diagnostic imaging, drug effects, 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

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