Longitudinal PET/CT evaluation of TNBS-induced inflammatory bowel disease rat model

Iria Seoane-Viaño; Noemí Gómez-Lado; Héctor Lázare-Iglesias; Manuel Barreiro-de Acosta; Jesús Silva-Rodríguez; Asteria Luzardo-Álvarez; Michel Herranz; Francisco Otero-Espinar; José Ramón Antúnez-López; María Jesús Lamas; Pablo Aguiar; Anxo Fernández-Ferreiro; Álvaro Ruibal

doi:10.1016/j.ijpharm.2018.08.005

Longitudinal PET/CT evaluation of TNBS-induced inflammatory bowel disease rat model

Int J Pharm. 2018 Oct 5;549(1-2):335-342. doi: 10.1016/j.ijpharm.2018.08.005. Epub 2018 Aug 3.

Affiliations

¹ Pharmacy and Pharmaceutical Technology Department and Industrial Pharmacy Institute, Faculty of Pharmacy, Universidade de Santiago de Compostela (USC), Campus Vida, Santiago de Compostela 15782, Spain.
² Molecular Imaging Group, Department of Psiquiatry, Radiology and Public Health, Faculty of Medicine, Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain; Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
³ Pathology Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain.
⁴ Gastroenterology Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain.
⁵ Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
⁶ Pharmacy Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
⁷ Molecular Imaging Group, Department of Psiquiatry, Radiology and Public Health, Faculty of Medicine, Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain; Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Nuclear Medicine Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain.
⁸ Pharmacy Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain. Electronic address: anxordes@gmail.com.
⁹ Molecular Imaging Group, Department of Psiquiatry, Radiology and Public Health, Faculty of Medicine, Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain; Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, Santiago de Compostela 15706, Spain; Nuclear Medicine Department, University Clinical Hospital Santiago de Compostela (SERGAS) (CHUS), Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Tejerina Foundation, José Abascal 40, Madrid 28003, Spain. Electronic address: alvaro.ruibal.morell@sergas.es.

PMID: 30081226
DOI: 10.1016/j.ijpharm.2018.08.005

Abstract

Inflammatory bowel disease (IBD) is a group of chronic disorders of the gastrointestinal tract, which two main types are Crohn's disease and ulcerative colitis. It has multifactorial etiologies, being essential the use of animal models and disease activity measures to develop new therapies. With this aim, the use of animal models in combination with non-invasive molecular imaging can play an important role in the development of new treatments. In this study, IBD was induced in rats using 2,4,6-trinitrobenzenesulfonic acid (TNBS) and longitudinal [¹⁸F]FDG PET/CT scans were conducted to assess disease progression post-TNBS administration. Afterwards, [¹⁸F]FDG PET/CT scans were carried out after treatment with methylprednisolone to validate the model. In non-treated rats, SUV_max (Standardized Uptake Value) rapidly increased after IBD induction, being particularly significant (p < 0.01) on days 7-13 after induction. There were no significant differences between non-treated and treated IBD rats from days 0-3. Nevertheless, treated IBD rats showed a significant decrease in SUV_max between days 7-13 (p < 0.01). Histological examination showed descending and transverse colon as the most affected regions. There was a moderate (R² = 0.61) and strong (R² = 0.82) correlation of SUV_max with Nancy grade (parameter for histological assessment of disease activity) and weight changes, respectively. In this study, we have performed the first longitudinal [¹⁸F]FDG PET/CT assessment of TNBS-induced IBD in rats, demonstrating the potential role of preclinical molecular imaging for the evaluation of new therapies in combination with IBD rat models.

Keywords: Colitis; Inflammatory bowel disease; Rat model; TNBS-induced; [(18)F]FDG PET.

Publication types

Validation Study

MeSH terms

Animals
Colitis / chemically induced
Colitis / diagnostic imaging*
Colitis / pathology
Colon / diagnostic imaging*
Colon / pathology
Disease Models, Animal
Disease Progression
Fluorodeoxyglucose F18 / administration & dosage
Inflammatory Bowel Diseases / chemically induced
Inflammatory Bowel Diseases / diagnostic imaging*
Inflammatory Bowel Diseases / pathology
Male
Molecular Imaging / methods*
Positron Emission Tomography Computed Tomography*
Predictive Value of Tests
Radiopharmaceuticals / administration & dosage
Rats, Sprague-Dawley
Reproducibility of Results
Time Factors
Trinitrobenzenesulfonic Acid*
Weight Loss

Substances

Radiopharmaceuticals
Fluorodeoxyglucose F18
Trinitrobenzenesulfonic Acid