Open AccessThe Imaging of Insulinomas Using a Radionuclide-Labelled Molecule of the GLP-1 Analogue Liraglutide: A New Application of Liraglutide
Author(s) -
Jing Lv,
Yu Pan,
Xiao Li,
Dengfeng Cheng,
Shuai Liu,
Hongcheng Shi,
Yifan Zhang
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0096833
Subject(s) - liraglutide , insulinoma , in vivo , emission computed tomography , nuclear medicine , positron emission tomography , molecular imaging , preclinical imaging , spect imaging , medicine , endocrinology , chemistry , pancreas , biology , type 2 diabetes , diabetes mellitus , microbiology and biotechnology
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 125 I-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 125 I by the Iodogen method. The labelled 125 I-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 125 I-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 125 I was successful, yielding a labelling rate of approximately 95% and a radiochemical purity of greater than 95%. For the binding between 125 I-liraglutide and the GLP-1 receptor on the surface of INS-1 cells, the equilibrium dissociation constant (K d ) was 128.8±30.4 nmol/L(N = 3), and the half-inhibition concentration (IC 50 ) was 542.4±187.5 nmol/L(N = 3). Small-animal SPECT/CT imaging with 125 I-liraglutide indicated that the tumour imaging was clearest at 90 min after the 125 I-liraglutide treatment. An examination of the in vivo distribution of radioactivity revealed that at 90 min after the 125 I-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 125 I-liraglutide was predominantly metabolised and cleared by the liver and kidneys. Conclusion The radionuclide 125 I-liraglutide can be utilised for the specific imaging of insulinomas, representing a new non-invasive approach for the in vivo diagnosis of insulinomas.