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

Parasuraman Padmanabhan, Johannes Grosse, Abu Bakar Md Ali Asad, George K. Radda, Xavier Golay

Research output: Contribution to journalArticle

Abstract

Background: Gastrointestinal (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). Methods: Tc-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. Results: The 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). Conclusion: Here, 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.

Original languageEnglish (US)
JournalEJNMMI Research
Volume3
Issue number1
DOIs
StatePublished - 2013
Externally publishedYes

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Gastrointestinal Transit
Pentetic Acid
Charcoal
Loperamide
Transverse Colon
Cecum
Rectum
Trypan Blue
Single-Photon Emission-Computed Tomography
Radioactivity
Technetium Tc 99m Pentetate
Physiological Phenomena
Descending Colon
Flatulence
Ascending Colon
Gastrointestinal Motility
Defecation
Irritable Bowel Syndrome
Technetium
Appetite

Keywords

  • Bowel disorder
  • GI transit
  • Loperamide
  • SPECT-CT
  • Tc-Ch-DTPA

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT. / Padmanabhan, Parasuraman; Grosse, Johannes; Asad, Abu Bakar Md Ali; Radda, George K.; Golay, Xavier.

In: EJNMMI Research, Vol. 3, No. 1, 2013.

Research output: Contribution to journalArticle

Padmanabhan, Parasuraman ; Grosse, Johannes ; Asad, Abu Bakar Md Ali ; Radda, George K. ; Golay, Xavier. / Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT. In: EJNMMI Research. 2013 ; Vol. 3, No. 1.
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N2 - Background: Gastrointestinal (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). Methods: Tc-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. Results: The 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). Conclusion: Here, 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.

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