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Gelatin-Based Plasma Expander Effectively Reduces Renal Uptake of ¹¹¹In-Octreotide in Mice and Rats

¹ Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; ² Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; and ³ Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence: For correspondence or reprints contact: Julliëtte E.M. van Eerd, Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: j.vaneerd{at}nucmed.umcn.nl

¹¹¹In-Diethylenetriaminepentaacetic acid-octreotide generally is used for the scintigraphic imaging of neuroendocrine and other somatostatin receptor–positive tumors. On the basis of the successful targeting of octreotide, radiolabeled somatostatin analogs, such as ⁹⁰Y-(1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid [DOTA])⁰-Tyr³-octreotide and ¹⁷⁷Lu-DOTA⁰-Tyr³-octreotate, were developed for peptide receptor radionuclide therapy. However, the maximum tolerated doses of these analogs are limited because of the high and persistent renal uptake that leads to relatively high radiation doses in the kidneys. Renal uptake can be reduced by coinfusion of basic amino acids or polypeptides. However, high doses of basic amino acids can induce severe side effects. It was reported that the infusion of gelatin-based plasma expanders resulted in increased low-molecular-weight proteinuria, suggesting that these plasma expanders interfere with the tubular reabsorption of peptides and proteins. In the present study, we analyzed the effects of several plasma expanders on the renal uptake of ¹¹¹In-octreotide in rats and mice. Methods: Wistar rats and BALB/c mice were injected with 0.5 or 0.1 mL of plasma expander, respectively. Thereafter, the animals received ¹¹¹In-octreotide intravenously. Animals were killed at 20 h after the injection of the radiopharmaceutical. Organs were dissected, and the amount of radioactivity in the organs and tissues was measured. Results: The administration of 20 mg of Gelofusine in rats or 4 mg in mice was as effective in reducing the renal uptake of ¹¹¹In-octreotide as the administration of 80 or 20 mg of lysine in rats or mice, respectively, without reducing ¹¹¹In-octreotide uptake in receptor-positive organs. Plasma expanders based on starch or dextran had no effect on the renal uptake of ¹¹¹In-octreotide. Conclusion: The gelatin-based plasma expander Gelofusine significantly reduced the kidney uptake of ¹¹¹In-octreotide as effectively as did lysine. Because Gelofusine is a well-known and generally used blood volume substitute that can be applied safely without the induction of toxicity, evaluation of this compound for its potential to reduce the kidney uptake of radiolabeled peptides in patients is warranted.

Key Words: renal reabsorption • plasma expander • octreotide • kidney

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