Succinylated gelatin improves the theranostic potential of radiolabeled exendin-4 in insulinoma patients
| Autor: | Tom J.P. Jansen, Damian Wild, Marti Boss, Marcel J.R. Janssen, Wietske Woliner-van der Weg, Inge van der Kroon, Martin Gotthardt, Eric P. Visser, Mijke Buitinga, Maarten Brom, Erik H.J.G. Aarntzen, Martin Béhé |
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| Rok vydání: | 2018 |
| Předmět: |
Agonist
Adult Male endocrine system Single Photon Emission Computed Tomography Computed Tomography medicine.drug_class lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Gelofusine 030209 endocrinology & metabolism Kidney 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center 0302 clinical medicine Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] medicine Image Processing Computer-Assisted Dosimetry Humans Radiology Nuclear Medicine and imaging Insulinoma business.industry Other Research Radboud Institute for Health Sciences [Radboudumc 0] Indium Radioisotopes digestive oral and skin physiology Biological Transport Succinates medicine.disease 3. Good health medicine.anatomical_structure Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] 030220 oncology & carcinogenesis Absorbed dose Isotope Labeling Radionuclide therapy Exenatide Gelatin Female Pancreas Nuclear medicine business hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Nuclear Medicine (1978), 60, 812-816 Journal of Nuclear Medicine The Journal of Nuclear Medicine (1978), 60, 6, pp. 812-816 |
| ISSN: | 0161-5505 |
| Popis: | 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. ispartof: JOURNAL OF NUCLEAR MEDICINE vol:60 issue:6 pages:812-816 ispartof: location:United States status: Published online |
| Databáze: | OpenAIRE |
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