The Imaging of Insulinomas Using a Radionuclide-Labelled Molecule of the GLP-1 Analogue Liraglutide: A New Application of Liraglutide

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.