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  • Title: Reduction of renal uptake of radiolabeled octreotate by amifostine coadministration.
    Author: Melis M, Valkema R, Krenning EP, de Jong M.
    Journal: J Nucl Med; 2012 May; 53(5):749-53. PubMed ID: 22496587.
    Abstract:
    UNLABELLED: 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 PRRT with (177)Lu-DOTA,Tyr(3)-octreotate. This study describes the direct effect of amifostine on kidney and tumor uptake of (111)In-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 WR-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 PRRT using somatostatin analogs, both by mitigation of radiation damage and the currently observed reduction of absorbed kidney radiation dose.
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