Reduction of Renal Uptake of Radiolabeled Octreotate by Amifostine Coadministration

Marleen Melis, R. Valkema, Eric Krenning, Marion Jong

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Megalin-mediated renal retention of radiolabeled somatostatin analogs may lead to nephrotoxicity during peptide receptor radionuclide therapy (PRRT). The cytoprotective agent amifostine protected rats from long-term nephrotoxicity after PART with Lu-177-DOTA,Tyr(3)-octreotate. This study describes the direct effect of amifostine on kidney and tumor uptake of In-111-DOTA,Tyr(3)-octreotate. Methods: In vivo biodistribution studies were performed using CA20948 tumor-bearing rats, with or without amifostine coadministration, via several routes. In vitro uptake was studied in somatostatin receptor-expressing CA20948 and megalin or cubilin receptor-expressing BN-16 cells, in the absence or presence of amifostine or its active metabolite WA-1065. Results: Coadministration of amifostine decreased renal uptake of radiolabeled octreotate in vivo, whereas tumor uptake was not affected. In agreement, amifostine and WR-1065 coincubation reduced uptake in BN-16 but not in CA20948 cells. Conclusion: Amifostine may provide renal protection during PART using somatostatin analogs, both by mitigation of radiation damage and the currently observed reduction of absorbed kidney radiation dose.
Original languageUndefined/Unknown
Pages (from-to)749-753
Number of pages5
JournalJournal of Nuclear Medicine
Volume53
Issue number5
DOIs
Publication statusPublished - 2012

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