Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled octreotate in rats with CA20948 tumours

Marleen Melis, M Bijster, Marianne Visser, MW Konijnenberg, Jan de Swart, EJ Rolleman, OC Boerman, Eric Krenning, Marion Jong

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Abstract

Peptide receptor radionuclide therapy using beta-emitting radiolabelled somatostatin analogues like DOTA,Tyr(3)-octreotate shows beneficial results in patients suffering from somatostatin receptor overexpressing tumours. However, after high-dose therapy partial renal reabsorption of radiopeptides may lead to nephrotoxicity. Co-infusion of lysine/arginine lowers renal retention of these radiopeptides without affecting tumour uptake. Recently co-administration of Gelofusine has been described to have a comparable kidney-protecting effect in rats. In the present study optimal dosing of Gelofusine co-administration was studied in tumour-bearing rats. Doses of 40, 80, 120 or 160 mg/kg Gelofusine were co-injected with 15 A mu g DOTA,Tyr(3)-octreotate, labelled with 3 MBq In-111 for biodistribution (24 h post-injection, n = 4 per group) and with 60 MBq In-111 for microSPECT imaging experiments at 3, 24 and 48 h post-injection. An additional group of rats received 80 mg/kg Gelofusine plus 400 mg/kg lysine co-injection. Biodistribution studies were performed both in older (475 g) and younger (300 g) rats, the latter bearing CA20948 tumours. Co-injection of 40 mg/kg Gelofusine resulted in 40-50% reduction of renal uptake and retention of In-111-DOTA,Tyr(3)-octreotate, whereas higher doses further increased the reduction to 50-60% in both groups of rats. Combining Gelofusine and lysine caused 70% reduction of renal uptake. The uptake of radiolabelled octreotate both in somatostatin receptor-expressing normal tissues and tumours was not affected by Gelofusine co-injection. In rats co-injection of 80 mg/kg Gelofusine resulted in maximum reduction of renal retention of In-111-DOTA,Tyr(3)-octreotate, which was further improved when combined with lysine. Tumour uptake of radiolabelled octreotate was not affected, resulting in an increased tumour to kidney ratio.
Original languageUndefined/Unknown
Pages (from-to)1968-1976
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume36
Issue number12
DOIs
Publication statusPublished - 2009

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