Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Radiology, Nuclear Medicine & Medical Imaging, exendin-4, kidney uptake, insulinoma, radionuclide therapy, dosimetry, RECEPTOR RADIONUCLIDE THERAPY, GLUCAGON-LIKE PEPTIDE-1, BETA-CELL MASS, NEUROENDOCRINE TUMORS, SOMATOSTATIN ANALOG, RENAL UPTAKE, DOSIMETRY, QUANTIFICATION, RADIOTRACERS, TOMOGRAPHY, Adult, Biological Transport, Exenatide, Female, Gelatin, Humans, Image Processing, Computer-Assisted, Indium Radioisotopes, Insulinoma, Isotope Labeling, Kidney, Male, Single Photon Emission Computed Tomography Computed Tomography, Succinates, INNODIA - 115797;info:eu-repo/grantAgreement/EC/H2020/115797, 1103 Clinical Sciences, Nuclear Medicine & Medical Imaging, 3202 Clinical sciences

Abstract:

Being highly expressed in insulinomas, the glucagon-like peptide-1 receptor (GLP-1R) is a potential target for diagnosis, localization and treatment with the radiolabeled GLP-1R agonist exendin. Tracer accumulation in the kidneys, however, hampers accurate diagnostic visualization of pancreatic tissue and prohibits the therapeutic application of radiolabeled exendin for beta-cell-derived tumors. Therefore, we evaluated the ability of succinylated gelatin (Gelofusine) to reduce the renal accumulation of radiolabeled exendin in humans and we performed dosimetric calculations to estimate the maximum absorbed insulinoma dose that could be achieved when exendin would be used for peptide receptor radionuclide therapy. Methods: Ten healthy volunteers received 50 MBq 111In-exendin-4, in combination with Gelofusine or saline in a crossover design. SPECT/CT images were obtained after 24 hours. The procedure was repeated three weeks later. Uptake of 111In-exendin was determined by drawing regions of interest around the kidneys and in the pancreas. Planar scintigraphic 111In-exendin images of five insulinoma patients were used for dosimetry studies estimating the maximum insulinoma absorbed dose that could be achieved without causing radiotoxicity to other organs. Results: Gelofusine reduced the renal accumulation of 111In-exendin-4 with 18.1%, whereas the pancreatic uptake remained unchanged. In 3 out of 10 subjects, the kidney uptake was reduced to such an extent that the pancreatic tail could be better discriminated from the kidney signal. Dosimetric estimations suggested that the insulinoma absorbed dose ranges from 30.3-127.8 Gy. This dose could be further increased to maximally 156.1 Gy when Gelofusine would be used. Conclusion: We have shown that Gelofusine can reduce the renal accumulation of 111In-exendin-4 in humans. This reduction does not only allow more accurate qualitative and quantitative analyses of radiolabeled exendin uptake in the tail region of the pancreas, but it also potentiates the safe delivery of a higher radiation dose to GLP-1R positive tumors for therapy.