Validation of gastric-emptying scintigraphy of solids and liquids in mice using dedicated animal pinhole scintigraphy.
Gastric emptying in small laboratory animals is a useful parameter to assess gastrointestinal motility for physiologic, pharmacologic, or other research purposes. In mice, phenol red recovery is considered the gold standard for determination of gastric emptying. However, this method requires sacrifice of the animal and yields data of gastric emptying at only 1 time point. Gastric-emptying scintigraphy, the gold standard technique in humans, allows sequential and serial measurements in the same subject. In this study, we developed and validated a novel method of gastric-emptying scintigraphy applied in mice, by comparing it with phenol red photospectrometry.


METHODS
A dedicated animal pinhole gamma camera was equipped with a specially designed mouse application device. Gastric emptying was measured in unanesthetized mice using pinhole scintigraphy. First, gastric emptying determined with scintigraphy was compared with gastric phenol red recovery simultaneously within the same population. Subsequently, normal values for gastric emptying of solids and liquids in mice were established, and finally, the effects of handling stress and the late effects of frequently used anesthetics or sedatives on gastric emptying were assessed by scintigraphy.


RESULTS
Gastric emptying of liquids measured by pinhole scintigraphy did not significantly differ from that measured by phenol red recovery. For the same information, 80% fewer animals were needed for the scintigraphic method. More stress-related delay in gastric emptying was induced by multiple handling of the mice, compared with the less frequent handling that was associated with taking measurements every 10 min or more (P < 0.05). The mean half-emptying time for solids measured by scintigraphy was significantly slower than that for liquid emptying (P < 0.01). Previous anesthesia did not significantly affect gastric emptying 6 h after induction.


CONCLUSIONS
Dedicated small-animal pinhole gastric-emptying scintigraphy is a reliable tool to investigate gastrointestinal motility in mice, significantly reducing the number of laboratory animals needed for statistical power in trials. The technique enables sequential and serial measurement within 1 subject and is thus useful for follow-up investigations, which can be performed even after invasive procedures that require anesthesia.
Bennink
Roelof J
RJ
Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands. r.bennink@amc.uva.nl
De Jonge
Wouter J
WJ
Symonds
Erin L
EL
van den Wijngaard
Rene M
RM
Spijkerboer
Astrid L
AL
Benninga
Marc A
MA
Boeckxstaens
Guy E
GE
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D005240:Feasibility Studies; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D006234:Handling, Psychological; D051379:Mice; D008807:Mice, Inbred BALB C; D010637:Phenolsulfonphthalein / Q000008:administration & dosage; D010812:Physical Stimulation; D011877:Radionuclide Imaging; D013053:Spectrophotometry / Q000379:methods; D013270:Stomach / Q000000981:diagnostic imaging* / Q000502:physiology*; D013668:Technetium Tc 99m Aggregated Albumin / Q000493:pharmacokinetics
D000700:Analgesics; D013668:Technetium Tc 99m Aggregated Albumin; D010637:Phenolsulfonphthalein