Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT

Abstract

BackgroundGastrointestinal (GI) disorders are commonly associated with chronic conditions such as diabetes, obesity, and hypertension. Direct consequences are obstipation or diarrhea as opposite aspects of the irritable bowel syndrome, and more indirectly, alteration of appetite, feeling of fullness, flatulence, bloatedness, and eventually leading to altered absorption of nutrients. Moreover, GI retention and passage times have been recognized as important factors in determining the release site and hence the bioavailability of orally administered drugs. To facilitate the understanding of physiological and pathological processes involved, it is necessary to monitor the gut motility in animal models. Here, we describe a method for studying the GI transit time using technetium-labeled activated charcoal diethylenetriaminepentaacetic acid (99mTc-Ch-DTPA) detected by single-photon emission computed tomography (SPECT).MethodsTc-DTPA was adsorbed onto activated charcoal and administered orally to trypan blue-tainted (n = 4) 129SvEv mice (50 to 80 MBq/animal, n = 11). The exact distribution and movement of radioactivity in the gastrointestinal tract was measured at intervals of 1, 3, 6, 12, and 22 h by SPECT-CT. In addition, in order to validate the imaging of GI transient time, loperamide (0.25 mg/animal, n = 3) was used to delay the GI transit.ResultsThe transit time measured as the peak radioactivity occurring in the rectum was 6 to 7 h after gavaging of 99mTc-Ch-DTPA. After 1 h, the bolus had passed into the small intestine and entered the cecum and the colon. At 6 and 8 h, the cecum, the ascending, transverse, and descending colon, and the rectum showed significant labeling. Several pellets were stored in the rectum for defecation. After 22 h, little activity remained in the stomach and none was detected in the transverse colon or other GI locations. In contrast, 6 h after administration of loperamide, only the cecum and part of the transverse colon were labeled. After 22 h, both structures retained significant amount of label. This delay has been verified by non-radiolabeled dye trypan blue GI measurements (n = 4).ConclusionHere, we present the first non-invasive study of mouse GI transit time, allowing clear differentiation between vehicle- and loperamide-treated animals. This technique is useful for the investigation of GI motility in mice.

Diet and Feeding Pattern Affect the Diurnal Dynamics of the Gut Microbiome

“…< 0.05). Since it takes > 1 hour for a food bolus to reach the cecum (Padmanabhan et al, 2013), lower bar graphs show the average percent reads (± SEM, n = 9) for the dark/active feeding phase (ZT 17, 21, and 1), and the light/inactive fasting phase (ZT 5, 9, and 13). *p < 0.05.…”

“…Histogram (bottom left of each panel) show percent reads (± SEM, n = 9) that are expressed when light off/light on. Histogram (bottom right of each panel) show percent reads (± SEM, n = 9) that are expressed when food from nighttime feeding has reached the cecum (ZT 17, 21, 1) and during relative fasting (ZT 5, 9, 13; see Fig 2 and Padmanabhan et al, 2013). * p < 0.05.…”

“…For (C) the NA condition is excluded from the line plot but can be seen in Figure S4C. This is followed by a histogram of percent total reads (± SEM, n = 18) that this genus comprises in each condition, a histogram of percent reads (± SEM, n = 9) that are expressed when light off/light on and a histogram of percent reads (± SEM, n = 9) that are expressed when food from nighttime feeding has reached the cecum (ZT 17, 21, 1) and during relative fasting (ZT 5, 9, 13; see Fig 2 and Padmanabhan et al, 2013). …”

Efficient Norovirus and Reovirus Replication in the Mouse Intestine Requires Microfold (M) Cells

“…In addition, the intestinal transit time in mice is similar to the length of a replicative cycle of MNV (21,46). Therefore, we adapted the light-sensitive, neutral red (NR)-containing MNV (41) for in vivo studies.…”

Polylactide-Co-Glycolide Nanoparticles of Antitubercular Drugs: Formulation, Characterization and Biodistribution Studies

“…Polymeric nanoparticles can be used for scintigraphic imaging, after radiolabeling with a suitable γ-emitting radionuclide because of their low toxicity and surface characteristics [18]. For studying the biodistribution pattern of oral dosage forms, a nonabsorbable chelate of a radioactive isotope, technetium-diethylene triamine penta acetic acid (Tc-DTPA) is generally used, because technetium-99m ( 99m Tc) possesses low radiation dose and a short half-life of 6 h [19,20].…”