Abstract
1464
Objectives: Nephrotoxicity due to renal re-absorption (RRA) of radiolabeled peptides is limiting the tumor dose in peptide receptor radionuclidetherapy (PRRT). Therefore, we evaluated the ability of several agents to inhibit renal accumulation of different radiopeptides. Methods: Male wistar rats (4/group) where injected iv. with 1 MBq of 111In-Octreotide (OCT), -Minigastrin (MG), -Bombesin (BOM), or -Exendin (EX) together with a potential inhibitor of renal uptake (Arginine (Arg), Lysine (Lys), Poly-Glutamic acid (PGA), and Gelofusine (GF)) or PBS (control). In addition, albumin fragments <50kD (FRALB) were obtained by digestion with Trypsin for use as inhibitors. 20 h p.i. organ uptake was determined as %IA/g. Lys, PGA, and GF were also combined to determine whether an additive effect could be obtained. The localization of the peptides in the kidneys was investigated by autoradiography. Results: The level of kidney uptake of each peptide correlated with the number of charged amino acids. All radiopeptides were localized in the renal cortex as indicated by autoradiography. RRA of OCT could be inhibited by Lys, Arg, FRALB, and GF (by 40.7%-45.1%) while PGA was not effective. On the other hand, RRA of BO, MG, and EX could be inhibited by PGA, FRALB, and GF (15.4%-85.4%) while Lys was ineffective. The combination of GF and Lys showed additive effects in inhibiting RRA of OCT while PGA and GF had additive effects for the inhibition of RRA of EX. Conclusions: Inhibition of RRA of the radiopeptides tested could be achieved by either Lys or PGA. However, kidney uptake of non of the peptides could be inhibited by both at the same time, indicating that at least two different uptake mechanisms play a role. GF and FRALB were able to inhibit RRA of all radiopeptides tested. Additional experiments are needed to further elucidate these mechanisms and to optimize inhibition of RRA of radiopeptides to reduce kidney dose in PRRT.
- Society of Nuclear Medicine, Inc.