RT Journal Article
SR Electronic
T1 Succinylated Gelatin Improves the Theranostic Potential of Radiolabeled Exendin-4 in Insulinoma Patients
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 812
OP 816
DO 10.2967/jnumed.118.219980
VO 60
IS 6
A1 Buitinga, Mijke
A1 Jansen, Tom
A1 van der Kroon, Inge
A1 Woliner-van der Weg, Wietske
A1 Boss, Marti
A1 Janssen, Marcel
A1 Aarntzen, Erik
A1 Béhé, Martin
A1 Wild, Damian
A1 Visser, Eric
A1 Brom, Maarten
A1 Gotthardt, Martin
YR 2019
UL http://jnm.snmjournals.org/content/60/6/812.abstract
AB Being highly expressed in insulinomas, the glucagonlike 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 β-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 if exendin were to be used for peptide receptor radionuclide therapy. Methods: Ten healthy volunteers received 50 MBq of 111In-exendin-4, in combination with Gelofusine or saline, in a crossover design. SPECT/CT images were obtained after 24 h. The procedure was repeated 3 wk 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 5 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 by 18.1%, whereas the pancreatic uptake remained unchanged. In 3 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 to 127.8 Gy. This dose could be further increased to maximally 156.1 Gy if Gelofusine was used. Conclusion: We have shown that Gelofusine can reduce the renal accumulation of 111In-exendin-4 in humans. This reduction not only allows more accurate qualitative and quantitative analyses of radiolabeled exendin uptake in the tail region of the pancreas but also potentiates the safe delivery of a higher radiation dose to GLP-1R–positive tumors for therapy.