title: Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors: 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.
authors: Jesús
authors: J
authors: Silva-Rodríguez
authors: Molecular Imaging Research Group, Instituto de Investigaciones Sanitarias (IDIS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain.
authors: Lara
authors: L
authors: García-Varela
authors: 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.
authors: Esteban
authors: E
authors: López-Arias
authors: Nuclear Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela, Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain.
authors: Inés
authors: I
authors: Domínguez-Prado
authors: Nuclear Medicine Department, Complexo Hospitalario Universitario de Santiago de Compostela, Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain.
authors: Julia
authors: J
authors: Cortés
authors: Molecular Imaging Research Group, Instituto de Investigaciones Sanitarias (IDIS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain.
authors: Juan
authors: J
authors: Pardo-Montero
authors: Molecular Imaging Research Group, Instituto de Investigaciones Sanitarias (IDIS), Travesía da Choupana s/n, 15706, Santiago de Compostela, Galicia, Spain.
authors: Anxo
authors: A
authors: Fernández-Ferreiro
authors: 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.
authors: Álvaro
authors: Á
authors: Ruibal
authors: 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.
authors: Tomás
authors: T
authors: Sobrino
authors: 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.
authors: Pablo
authors: P
authors: Aguiar
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D019788:Fluorodeoxyglucose F18; D001569:Benzodiazepines
keywords: Benzodiazepines; Brain; Diazepam; Pet; Pharmacology; Preclinical