225Ac and 213Bi alpha-Particle-Emitter Therapy in Combination with SAHA and 17-AAG

Abstract

Alpha-particle emitter radiopharmaceutical therapy (alpha-RPT) is a promising approach to cancer therapy. Alpha-particles lead to highly disruptive and largely irreparable deoxy ribonucleic acid (DNA) double strand breaks capable of killing a cell with as few as one to two tracks through the nucleus. Although the ability to repair alpha-induced DNA damage is independent of alpha-dose-rate the efficacy of alphaemitter with a long half-life can be compromised when targeting very rapidly proliferating tumor cells if the dose-rate is outpaced by the proliferation rate. In this study, we investigate alpha-particle emitter radiopharmaceutical therapy (alpha-RPT) using 225Ac (T1/2=10 days) and 213Bi (T1/2=45.6 min) in combination with clinically approved tumor growth suppressor, suberoylanilide hydroxamic acid (SAHA) and cell cycle blocker, 17-(Allylamino)-17-demethoxy- geldanamycin (17-AAG) in breast cancer cells.