Gelatin-based plasma expander effectively reduces renal uptake of In-111-labeled peptides

Abstract

1912

Objectives: Radiation nephritis is the dose limiting toxicity in most patients undergoing peptide receptor radionuclide therapy (PRRT). The high and persistent renal uptake of peptides labeled with radiometals causes high radiation doses to the kidneys. Renal uptake can be reduced by co-infusion of basic amino acids or polypeptides. However, high doses of basic amino acids can induce severe side effects. Recently, we observed that infusion of a low dose of gelatin-based plasma expanders increased urinary excretion of low molecular weight proteins. In this study we analyzed the effect of several plasma expanders on the renal uptake of ¹¹¹In-labeled peptides in rats.

Methods: Wistar rats were intravenously injected with 0.5 mL plasma expander. Immediately, thereafter, the animals received ¹¹¹In-labeled peptide intravenously (octreotide, exendin, minigastrin and bombesin). Animals were killed 20 h after the injection of the radiolabeled peptide. Organs were dissected and the concentration of radioactivity in the organs and tissues was determined.

Results: Administration of 0.5 ml Gelofusine^® in rats reduced the renal uptake of ¹¹¹In-octreotide and ¹¹¹In-minigastrin with 47% and 45% respectively. In contrast, the renal uptake of ¹¹¹In-labeled exendin and bombesin were not reduced significantly. Plasma expanders based on starch or dextran showed no effect on renal uptake of ¹¹¹In-octreotide. Evaluation of Gelofusin^® for its potential to reduce kidney uptake of radiolabeled peptides in patients is required. Evaluation in healthy volunteers showed reduced renal uptake of ¹¹¹In-Octreotide after infusion of Gelofusine^®.

Conclusions: Gelatin-based plasma expander Gelofusine^® reduced the kidney uptake of ¹¹¹In-octreotide and ¹¹¹In-minigastrin as effectively as a high dose of lysine (80 mg). Gelofusine^® is a well-known and generally used blood volume substitute that can be applied safely without induction of toxicity. A first clinical study in healthy volunteers that received Gelofusin^® before injection of ¹¹¹In-Octreotide, confirmed our preclinical findings.