Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

Jesús Silva-Rodríguez; Lara García-Varela; Esteban López-Arias; Inés Domínguez-Prado; Julia Cortés; Juan Pardo-Montero; Anxo Fernández-Ferreiro; Álvaro Ruibal; Tomás Sobrino; Pablo Aguiar

doi:10.1016/j.nucmedbio.2016.09.001

Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

Nucl Med Biol. 2016 Dec;43(12):827-834. doi: 10.1016/j.nucmedbio.2016.09.001. Epub 2016 Sep 10.

Affiliations

¹ Molecular Imaging Research Group, Instituto de Investigaciones Sanitarias (IDIS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain. Electronic address: jesus.silva@gmx.es.
² Molecular Imaging Research Group, Instituto de Investigaciones Sanitarias (IDIS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain.
³ Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Universidade de Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain.
⁴ Nuclear Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela, Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain.
⁵ Molecular Imaging Research Group, Instituto de Investigaciones Sanitarias (IDIS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain; Nuclear Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela, Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain; In Vivo Molecular Imaging and Medical Physics Group, Facultade de Medicina, Universidade Santiago Compostela (USC), Rúa de San Francisco s/n, 15782, Santiago de Compostela, Galicia, Spain; Fundación Tejerina. Calle José Abascal 40, 28003, Madrid, Spain.
⁶ Molecular Imaging Research Group, Instituto de Investigaciones Sanitarias (IDIS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain; In Vivo Molecular Imaging and Medical Physics Group, Facultade de Medicina, Universidade Santiago Compostela (USC), Rúa de San Francisco s/n, 15782, Santiago de Compostela, Galicia, Spain.

PMID: 27792990
DOI: 10.1016/j.nucmedbio.2016.09.001

Abstract

Introduction: Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework.

Aim: This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats.

Methods: Twelve Sprague-Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups.

Results: Our analysis revealed a significant reduction of global FDG uptake after acute (-16.2%) and chronic (-23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p<0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam.

Conclusions: The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this medication.

Keywords: Benzodiazepines; Brain; Diazepam; Pet; Pharmacology; Preclinical.

MeSH terms

Animals
Benzodiazepines / administration & dosage*
Benzodiazepines / pharmacology*
Biological Transport / drug effects
Brain / diagnostic imaging*
Brain / drug effects*
Brain / metabolism
Fluorodeoxyglucose F18* / metabolism
Positron-Emission Tomography*
Rats
Rats, Sprague-Dawley
Time Factors

Substances

Fluorodeoxyglucose F18
Benzodiazepines