title: Pancreas and liver uptake of new radiolabeled incretins (GLP-1 and Exendin-4) in models of diet-induced and diet-restricted obesity.
abstract: BACKGROUND
  Radiolabeled GLP-1 and its analog Exendin-4, have been employed in diabetes and insulinoma. No protocol in conventional Diet-Induced Obesity (DIO), and Diet-Restricted Obesity (DRO), has been identified. Aiming to assess pancreatic beta cell uptake in DIO and DRO, a protocol was designed.
  
  
  METHODS
  GLP-1-βAla-HYNIC and HYNIC-βAla-Exendin-4 were labeled with technetium-99m. Four Swiss mouse models were adopted: Controls (C), Alloxan Diabetes Controls (ADC), DIO and DRO. Biodistribution and ex-vivo planar imaging were documented.
  
  
  RESULTS
  Radiolabeling yield was in the range of 97% and both agents were hydrophilic. Fasting Blood Glucose (FBG) was 79.2±8.2mg/dl in C, 590.4±23.3mg/dl in ADC, 234.3±66.7mg/dl in DIO, and 96.6±9.3 in DRO (p=0.010). Biodistribution confirmed predominantly urinary excretion. DIO mice exhibited depressed uptake in liver and pancreas, for both radiomarkers, in the range of ADC. DRO only partially restored such values.99mTc-HYNIC-βAla-Exendin-4 demonstrated better results than GLP-1-βAla-HYNIC-99mTc.
  
  
  CONCLUSIONS
  1) Diet-induced obesity remarkably depressed beta cell uptake; 2) Restriction of obesity failed to normalize uptake, despite robust improvement of FBG; 3) HYNIC-βAla-Exendin-4 was the most useful marker; 4) Further studies are recommended in obesity and dieting, including bariatric surgery.
authors.affiliation: Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes, 2242, São Paulo, 05508-000, Brazil. Electronic address: danyseo@uol.com.br.
authors.forename: Daniele
authors.initials: D
authors.lastname: Seo
authors.affiliation: Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes, 2242, São Paulo, 05508-000, Brazil.
authors.forename: Bluma Linkowski
authors.initials: BL
authors.lastname: Faintuch
authors.affiliation: School of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 580, Bloco 17, São Paulo, 05508-900, Brazil.
authors.forename: Erica
authors.initials: E
authors.lastname: Aparecida de Oliveira
authors.affiliation: Department of Gastroenterology, Hospital das Clínicas, Av. Enéas C. Aguiar, 255, 9th Floor, Rm 9077, São Paulo, 05403-900, Brazil.
authors.forename: Joel
authors.initials: J
authors.lastname: Faintuch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism* / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism*; D010179:Pancreas / Q000000981:diagnostic imaging / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014688:Venoms / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
keywords: Diabetes; Diagnostic imaging; GLP-1 analogs; Metabolic surgery; Obesity; Technetium-99m