Layered Nanoparticles for Targeted Alpha Generator Radiotherapy

David Robertson (U Missouri)
Event Date and Time: 
Thu, 2015-10-22 14:00 - 15:00
TRIUMF Auditorium

Targeted radiotherapies based on alpha emitters are a promising alternative to beta emitting radionuclides. Because of their much shorter range, targeted alpha-radiotherapy (TAT) agents have great potential for application to small, disseminated tumors and micro metastases and treatment of hematological malignancies consisting of individual, circulating neoplastic cells. A promising approach to TAT is the use of the in vivo alpha-generator radionuclides 223Ra (t1/2 = 11.4 d) and 225Ac (t1/2 = 10.0 d). In addition to their longer half-lives, these two isotopes have the potential of dramatically increasing the therapeutic efficacy of the endoradiotherapy as they each emit four alpha-particles in their decay chain. This principle has recently been exploited in the development of Xofigo(R), the first TAT agent approved for clinical use by the U.S. Food and Drug Administration. Xofigo(R), formulated as 223RaCl2, is used for treatment of metastatic bone cancer in men with castration-resistant prostate cancer. Targeted therapy with 223Ra works in the case of bone cancer because radium, as a chemical analogue of calcium, efficiently targets bone. Further, the 223Ra decay daughters are either short lived or also have affinity for bone, limiting their movement into general circulation to damage non-target tissue. In order to bring the benefits of TAT with 223Ra or 225Ac to other tumor types, a new delivery method must be devised. This talk will focus on our development of a multilayered nanoparticle-antibody conjugate that can deliver multiple alpha radiations from the in vivo alpha-generator 225Ac at biologically relevant receptor sites.

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