Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled octreotate in rats with CA20948 tumours
Purpose: Peptide receptor radionuclide therapy using β-emitting radiolabelled somatostatin analogues like DOTA,Tyr3-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. Methods: Doses of 40, 80, 120 or 160 mg/kg Gelofusine were co-injected with 15 μg DOTA,Tyr3-octreotate, labelled with 3 MBq111In for biodistribution (24 h post-injection, n=4 per group) and with 60 MBq111In 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. Results: Co-injection of 40 mg/kg Gelofusine resulted in 40-50% reduction of renal uptake and retention of111In-DOTA,Tyr3-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. Conclusion: In rats co-injection of 80 mg/kg Gelofusine resulted in maximum reduction of renal retention of111In-DOTA,Tyr3- 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.
|Keywords||Kidney, Radiolabelled octreotate, Renal reabsorption, Succinylated gelatin|
|Persistent URL||dx.doi.org/10.1007/s00259-009-1196-8, hdl.handle.net/1765/24164|
|Journal||European Journal of Nuclear Medicine and Molecular Imaging|
Melis, M.L, Bijster, M, de Visser, M, Konijnenberg, M.W, de Swart, J, Rolleman, E.J, … de Jong, M. (2009). Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled octreotate in rats with CA20948 tumours. European Journal of Nuclear Medicine and Molecular Imaging, 36(12), 1968–1976. doi:10.1007/s00259-009-1196-8