Abstract
507
Objectives 111In-DOTA-RGD tetramer exhibited high tumor uptake and long tumor retention in integrin αvβ3-positive tumors. We evaluated the therapeutical efficacy of 90Y-DOTA-RGD tetramer (RGD4) in U87MG tumor model.
Methods Maximum tolerated dose (MTD) in nontumor-bearing nude mice was determined by i.v injection of escalating doses of 90Y-DOTA-RGD4 (0.3, 0.5, 0.8, 1.2, and 1.8 mCi). Body weight and health status were determined twice weekly over 20 days. Peripheral blood was collected and tested by blood analyzer twice weekly. In the therapy studies, 90Y-DOTA-RGD4 was i.v administrated into U87MG tumor-bearing mice at the doses of 0.8 mCi and 1.2 mCi, while using cold RGD tetramer as controls. Histopathologic analyses were performed on liver and kidney tissues.
Results Only the 1.8 mCi group experienced animal death on 17 d postinjection. The body weight, as well as peripheral blood counts displayed an activity-dependant decline, but all values rebounded to baseline by 20 d p.i. 0.8-1.2 mCi of 90Y-DOTA-RGD4 was an appropriate dose for single dose therapy in nude mice according to the MTD study. With respect to therapy studies, the tumors in control group showed fast growth, whereas the tumors in therapy groups showed no growth by 20 d posttreatment, then displayed the dose-dependant tumor inhibition. There was no obvious liver and kidney damage to mice as determined by histopathology.
Conclusions The preliminary experimental data revealed the potential of 90Y-DOTA-RGD tetramer as a therapeutical agent for integrin αvβ3-positive tumors. The detailed therapeutical study, including 90Y-labeled nonsense peptide, is in progress.
- © 2009 by Society of Nuclear Medicine