PT  - JOURNAL ARTICLE
AU  - Buitinga, Mijke
AU  - Jansen, Tom
AU  - van der Kroon, Inge
AU  - Woliner-van der Weg, Wietske
AU  - Boss, Marti
AU  - Janssen, Marcel
AU  - Aarntzen, Erik
AU  - Béhé, Martin
AU  - Wild, Damian
AU  - Visser, Eric
AU  - Brom, Maarten
AU  - Gotthardt, Martin
TI  - Succinylated Gelatin Improves the Theranostic Potential of Radiolabeled Exendin-4 in Insulinoma Patients
AID  - 10.2967/jnumed.118.219980
DP  - 2019 Jun 01
TA  - Journal of Nuclear Medicine
PG  - 812--816
VI  - 60
IP  - 6
4099  - http://jnm.snmjournals.org/content/60/6/812.short
4100  - http://jnm.snmjournals.org/content/60/6/812.full
SO  - J Nucl Med2019 Jun 01; 60
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.