Nephrotoxicity due to renal reabsorption of radiolabeled peptides limits the tumor dose in peptide receptor radiotherapy (PRRT). Therefore, we evaluated the ability of several agents to inhibit the renal accumulation of different radiopeptides. Methods: Male Wistar rats (4 per group) were injected intravenously with 1 MBq of111In-labeled octreotide (OCT), minigastrin (MG), bombesin (BOM), or exendin (EX), together with a potential inhibitor of renal uptake (lysine [Lys], poly-glutamic acid [PGA], and Gelofusine [GF], a gelatin-based plasma expander) or phosphate-buffered saline as a control. Organ uptake at 20 h after injection was determined as the percentage of injected activity per gram (%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 using a phosphor imager. Results: OCT accumulation in the kidney was inhibited by Lys and GF (40.7%-45.1%), whereas PGA was ineffective. On the other hand, renal uptake of BOM, MG,and EX was inhibited by PGA and GF (15.4%-85.4%), whereas Lys was ineffective. The combination of GF and Lys showed additive effects in inhibiting OCT uptake, whereas PGA and GF had additive effects for the inhibition of EX uptake. The amount of kidney uptake correlated with the number of charged amino acids. All radiopeptides were localized in the renal cortex, as indicated by autoradiography. Conclusion: Inhibition of renal accumulation of the radiopeptides tested could be achieved by either Lys or PGA but not by both at the same time, suggesting 2 different uptake mechanisms. The differences in renal accumulation of radiopeptides may be related to the number of charges of a molecule. GF is the only compound that inhibited renal accumulation of all radiopeptides tested. Additional experiments are needed to further elucidate these findings and to optimize inhibition of renal accumulation of radiopeptides to reduce the kidney dose in PRRT. Copyright

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The Journal of Nuclear Medicine
Erasmus MC: University Medical Center Rotterdam

Gotthardt, M., van Eerd-Vismale, J., Oyen, W., de Jong, M., Zhang, H., Rolleman, E., … Boerman, O. (2007). Indication for different mechanisms of kidney uptake of radiolabeled peptides. The Journal of Nuclear Medicine, 48(4), 596–601. doi:10.2967/jnumed.106.036020