Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT
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 fullne...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2014
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/100194 http://hdl.handle.net/10220/18454 |
| _version_ | 1826112876051431424 |
|---|---|
| author | Padmanabhan, Parasuraman Grosse, Johannes Asad, Abu Bakar Md Ali Golay, Xavier Radda, George K. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Padmanabhan, Parasuraman Grosse, Johannes Asad, Abu Bakar Md Ali Golay, Xavier Radda, George K. |
| author_sort | Padmanabhan, Parasuraman |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:14:16Z |
| format | Journal Article |
| id | ntu-10356/100194 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:14:16Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1001942022-02-16T16:31:02Z Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT Padmanabhan, Parasuraman Grosse, Johannes Asad, Abu Bakar Md Ali Golay, Xavier Radda, George K. Lee Kong Chian School of Medicine (LKCMedicine) Medicine 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. Published version 2014-01-13T02:32:43Z 2019-12-06T20:18:12Z 2014-01-13T02:32:43Z 2019-12-06T20:18:12Z 2013 2013 Journal Article Padmanabhan, P., Grosse, J., Asad, A. B. M. A., Radda, G. K., & Golay, X. (2013). Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT. EJNMMI Research, 3(1), 60-. 2191-219X https://hdl.handle.net/10356/100194 http://hdl.handle.net/10220/18454 10.1186/2191-219X-3-60 23915679 en EJNMMI research © 2013 The Authors (licensee Springer). This paper was published in EJNMMI Research and is made available as an electronic reprint (preprint) with permission of the authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1186/2191-219X-3-60]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf |
| spellingShingle | Medicine Padmanabhan, Parasuraman Grosse, Johannes Asad, Abu Bakar Md Ali Golay, Xavier Radda, George K. Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT |
| title | Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT |
| title_full | Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT |
| title_fullStr | Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT |
| title_full_unstemmed | Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT |
| title_short | Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT |
| title_sort | gastrointestinal transit measurements in mice with 99mtc dtpa labeled activated charcoal using nanospect ct |
| topic | Medicine |
| url | https://hdl.handle.net/10356/100194 http://hdl.handle.net/10220/18454 |
| work_keys_str_mv | AT padmanabhanparasuraman gastrointestinaltransitmeasurementsinmicewith99mtcdtpalabeledactivatedcharcoalusingnanospectct AT grossejohannes gastrointestinaltransitmeasurementsinmicewith99mtcdtpalabeledactivatedcharcoalusingnanospectct AT asadabubakarmdali gastrointestinaltransitmeasurementsinmicewith99mtcdtpalabeledactivatedcharcoalusingnanospectct AT golayxavier gastrointestinaltransitmeasurementsinmicewith99mtcdtpalabeledactivatedcharcoalusingnanospectct AT raddageorgek gastrointestinaltransitmeasurementsinmicewith99mtcdtpalabeledactivatedcharcoalusingnanospectct |