Gelofusine reduced kidney uptake of radiolabeled exendin-4 by 18% in humans without affecting tumor-targeting, improving both diagnostic imaging and the feasibility of targeted radiation therapy for insulinomas.
18.1% kidney reductionGelofusine reduced renal accumulation of radiolabeled exendin-4 without affecting pancreatic/tumor uptake — improving the diagnostic window and potentially enabling therapeutic radiation doses up to 156 Gy for insulinomas.
What the researchers found
Succinylated gelatin (Gelofusine) reduced kidney accumulation of the radiolabeled GLP-1 receptor peptide 111In-exendin-4 by 18.1% in humans without affecting pancreatic uptake. In 3 of 10 volunteers, the reduction was sufficient to better distinguish the pancreatic tail from kidney signal on SPECT/CT imaging. Dosimetric calculations from 5 insulinoma patients estimated that tumor radiation doses of 30.3-127.8 Gy could be achieved, potentially increasing to 156.1 Gy with Gelofusine — making peptide receptor radionuclide therapy feasible for GLP-1R-positive insulinomas.
Why it matters
Insulinomas (insulin-secreting pancreatic tumors) are often tiny and hard to find. Radiolabeled exendin-4 targets the GLP-1 receptor on these tumors for both imaging and potential radiation therapy. However, the kidneys absorb large amounts of the radioactive peptide, which limits both the diagnostic quality (kidney signal obscures the nearby pancreas) and therapeutic potential (kidney radiation toxicity limits the dose). Reducing kidney uptake with Gelofusine is a practical solution that improves both diagnosis and opens the door to targeted radiation therapy for these tumors.
The numbers in context
n=10 healthy volunteers · 18.1% kidney uptake reduction · Pancreatic uptake unchanged · 5 insulinoma patients for dosimetry · Tumor dose 30.3-127.8 Gy · Up to 156.1 Gy with Gelofusine
How the study worked
Crossover study: 10 healthy volunteers received 50 MBq of 111In-exendin-4 with either Gelofusine or saline, then switched 3 weeks later. SPECT/CT images were acquired at 24 hours. Kidney and pancreatic uptake were quantified by region-of-interest analysis. Dosimetric calculations were performed using planar scintigraphy data from 5 insulinoma patients to estimate maximum achievable tumor radiation doses with and without Gelofusine.
Who was studied
10 healthy volunteers in a crossover design plus 5 insulinoma patients for dosimetric calculations
What this study cannot tell us
The 18.1% kidney reduction, while statistically significant, is relatively modest — in only 3 of 10 subjects did it meaningfully improve pancreatic visualization. The dosimetric calculations are theoretical estimates based on 5 insulinoma patients, not actual therapeutic outcomes. The study used 111In labeling (for imaging), but therapeutic applications would require different radioisotopes (like 177Lu or 90Y), which may have different kidney kinetics. The healthy volunteer kidney data may not perfectly predict behavior in patients with tumors.
How to read the evidence
This is a well-designed human crossover study with internal controls (each subject serving as their own control). The volunteer data is robust, though the dosimetric projections from 5 patients are theoretical estimates rather than therapeutic outcomes. Published in the Journal of Nuclear Medicine, a top-tier nuclear medicine journal.
When this study was published
Published in 2019, this study remains relevant as radiolabeled exendin continues to be developed for insulinoma imaging and therapy. Gelofusine-based kidney protection strategies are now being explored for other radiolabeled peptide therapies as well.
The bigger picture
Peptide receptor radionuclide therapy (PRRT) has transformed the treatment of neuroendocrine tumors using somatostatin analogs like 177Lu-DOTATATE. Extending this approach to GLP-1R-positive tumors using exendin-based peptides is a logical next step, but kidney toxicity has been the primary barrier. This study demonstrates a practical, clinically available solution (Gelofusine is already used in hospitals) that could enable a new PRRT indication. It also contributes to the broader effort of making radiolabeled peptide therapies safer across all tumor types.
Questions still open
- Could higher or repeated Gelofusine doses achieve greater kidney protection without affecting tumor uptake?
- Would combining Gelofusine with other kidney protection strategies (amino acid infusion) produce additive benefits?
- What are the actual therapeutic outcomes when radiolabeled exendin with Gelofusine is used to treat insulinomas in clinical practice?
Common questions
What is radiolabeled exendin-4?
Why do the kidneys absorb so much of the radioactive peptide?
Read the original research
Succinylated Gelatin Improves the Theranostic Potential of Radiolabeled Exendin-4 in Insulinoma Patients.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 60(6), 812-816
Citation
Buitinga, Mijke; Jansen, Tom; van der Kroon, Inge; Woliner-van der Weg, Wietske; Boss, Marti; Janssen, Marcel; Aarntzen, Erik; Béhé, Martin; Wild, Damian; Visser, Eric; Brom, Maarten; Gotthardt, Martin. (2019). Succinylated Gelatin Improves the Theranostic Potential of Radiolabeled Exendin-4 in Insulinoma Patients.. Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 60(6), 812-816. https://doi.org/10.2967/jnumed.118.219980