Making Peptide-Based Tumor Imaging and Therapy Safer by Reducing Kidney Radiation from Exendin-4

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.

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.

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.

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.

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.