title: The imaging of insulinomas using a radionuclide-labelled molecule of the GLP-1 analogue liraglutide: a new application of liraglutide.
abstract: OBJECTIVE
  This study explores a new, non-invasive imaging method for the specific diagnosis of insulinoma by providing an initial investigation of the use of 125I-labelled molecules of the glucagon-like peptide-1 (GLP-1) analogue liraglutide for in vivo and in vitro small-animal SPECT/CT (single-photon emission computed tomography/computed tomography) imaging of insulinomas.
  
  
  METHODS
  Liraglutide was labelled with 125I by the Iodogen method. The labelled 125I-liraglutide compound and insulinoma cells from the INS-1 cell line were then used for in vitro saturation and competitive binding experiments. In addition, in a nude mouse model, the use of 125I-liraglutide for the in vivo small-animal SPECT/CT imaging of insulinomas and the resulting distribution of radioactivity across various organs were examined.
  
  
  RESULTS
  The labelling of liraglutide with 125I was successful, yielding a labelling rate of approximately 95% and a radiochemical purity of greater than 95%. For the binding between 125I-liraglutide and the GLP-1 receptor on the surface of INS-1 cells, the equilibrium dissociation constant (Kd) was 128.8 ± 30.4 nmol/L(N = 3), and the half-inhibition concentration (IC50) was 542.4 ± 187.5 nmol/L(N = 3). Small-animal SPECT/CT imaging with 125I-liraglutide indicated that the tumour imaging was clearest at 90 min after the 125I-liraglutide treatment. An examination of the in vivo distribution of radioactivity revealed that at 90 min after the 125I-liraglutide treatment, the target/non-target (T/NT) ratio for tumour and muscle tissue was 4.83 ± 1.30(N = 3). Our study suggested that 125I-liraglutide was predominantly metabolised and cleared by the liver and kidneys.
  
  
  CONCLUSIONS
  The radionuclide 125I-liraglutide can be utilised for the specific imaging of insulinomas, representing a new non-invasive approach for the in vivo diagnosis of insulinomas.
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, School of Medicine, Fudan University, Shanghai, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007340:Insulinoma / Q000000981:diagnostic imaging* / Q000473:pathology; D007457:Iodine Radioisotopes / Q000737:chemistry; D051379:Mice; D010455:Peptides / Q000737:chemistry; D011859:Radiography; D011868:Radioisotopes / Q000737:chemistry; D018027:Receptors, Glucagon / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007457:Iodine Radioisotopes; D010455:Peptides; D011868:Radioisotopes; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1