Abstract
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Objectives Preclinical imaging typically requires anaesthesia to reduce motion-related problems. For translational relevance this anaesthesia must not significantly alter the experimental outcome. This study reports on the effects of both anaesthetic and carrier gas upon the uptake of 18F-MISO in a preclinical model of hypoxic tumour.
Methods The effect of carrier gas and anaesthetic was studied in 6 groups (n=5) of CaNT bearing CBA mice using 18F-MISO (10 MBq, i.v bolus). Mice were anaesthetised with isoflurane in air, isoflurane in pure oxygen, with ketamine/xylazine (KX) or hypnorm/hypnovel (HH) whilst breathing air, or in the awake state whilst breathing air or pure oxygen. For the anaesthetised mice PET/CT imaging was performed for 2 hours post dosing (10 MBq, IV). All mice were killed at 2 hours post dosing for tracer quantitation, EF5 staining to measure hypoxia and autoradiography.
Results EF5 staining confirmed the presence of hypoxia and EF5 positive regions correlated with 18F-MISO autoradiography. Tumour-to-muscle ratio (TMR) by dissection for non-anaesthetised mice breathing air was 5.2±0.4. TMR was reduced significantly when both pure oxygen (1.7±0.2) or anaesthetics were introduced (2.2±0.4, 2.4±0.4 and 2.7±0.3 for isoflurane on room air, HH and KX, respectively). No further reduction was measured when isoflurane in pure oxygen was used (1.7±0.2).
Conclusions The use of anaesthetics and/or use of pure oxygen significantly reduces the uptake of 18F-MISO and provides a major confound that compromises the validity of studies of tracer uptake in the anaesthetised state. Great care must to be taken in the interpretation of results generated where anaesthesia has been used and a move towards the use of awake animals for such imaging may be required despite the complications this infers for dynamic analyses