PT  - JOURNAL ARTICLE
AU  - Marleen Melis
AU  - Roelf Valkema
AU  - Eric P. Krenning
AU  - Marion de Jong
TI  - Reduction of Renal Uptake of Radiolabeled Octreotate by Amifostine Coadministration
AID  - 10.2967/jnumed.111.098665
DP  - 2012 May 01
TA  - Journal of Nuclear Medicine
PG  - 749--753
VI  - 53
IP  - 5
4099  - http://jnm.snmjournals.org/content/53/5/749.short
4100  - http://jnm.snmjournals.org/content/53/5/749.full
SO  - J Nucl Med2012 May 01; 53
AB  - 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 177Lu-DOTA,Tyr3-octreotate. This study describes the direct effect of amifostine on kidney and tumor uptake of 111In-DOTA,Tyr3-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.