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Renal Uptake of Radiolabeled Octreotide in Human Subjects Is Efficiently Inhibited by Succinylated Gelatin

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, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence: For correspondence or reprints contact: Wim J.G. Oyen, MD, PhD, Department of Nuclear Medicine (444), Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: w.oyen{at}nucmed.umcn.nl

Peptide receptor–mediated radiotherapy of neuroendocrine and other somatostatin receptor–positive tumors with radiolabeled somatostatin analogs has been applied in several experimental settings. The kidneys are the organs responsible for dose-limiting toxicity attributable to the retention of radiolabeled octreotide in the renal cortex, leading to a relatively high radiation dose that may result in irreversible loss of kidney function. The administration of basic amino acids reduces renal uptake but does have significant side effects. We observed that gelatin-based plasma expanders induced tubular low-molecular-weight proteinuria in healthy volunteers, suggesting that components in these solutions can interfere with the tubular reabsorption of proteins and peptides. Here, we studied the effects of infusion of low doses of the plasma expander succinylated gelatin (GELO) on the renal uptake of ¹¹¹In-labeled octreotide (¹¹¹In-OCT). Methods: Five healthy volunteers were given ¹¹¹In-OCT, first in combination with normal saline and 2 wk later in combination with GELO. Scintigraphic images of the kidneys as well as blood and urine samples were analyzed. To exclude a nonspecific hemodynamic effect of the plasma expander, the procedure was repeated with 5 other volunteers who received the carbohydrate-based plasma expander hydroxyethyl starch (HES). Results: Low doses of GELO were able to effectively reduce the kidney retention of ¹¹¹In-OCT. The renal radiation dose was significantly reduced by 45% ± 10% (mean ± SD) (P = 0.006), whereas HES showed no significant effect (0% ± 12%). The infusion of GELO did not cause any side effects. Conclusion: GELO effectively reduces the renal uptake of ¹¹¹In-OCT. In contrast to currently used mixtures of amino acids, GELO does not cause any side effects.

Key Words: radiolabeled octreotide • succinylated gelatin • kidneys

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