APS April Meeting 2014
Volume 59, Number 5
Saturday–Tuesday, April 5–8, 2014;
Savannah, Georgia
Session H3: Invited Session: Frontiers of the Interface Between Physics and Medicine
8:30 AM–10:18 AM,
Sunday, April 6, 2014
Room: Chatham Ballroom B
Sponsoring
Units:
DNP DPB
Chair: Jerry Nolen, Argonne National Laboratories
Abstract ID: BAPS.2014.APR.H3.1
Abstract: H3.00001 : New Methods for Targeted Alpha Radiotherapy
8:30 AM–9:06 AM
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Abstract
Author:
J. David Robertson
(University of Missouri-Columbia)
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 \textit{in vivo} $\alpha
$-generator radionuclides $^{\mathrm{223}}$Ra (t$_{\mathrm{1/2}} \quad =$ 11.4
d) and $^{\mathrm{225}}$Ac (t$_{\mathrm{1/2}} \quad =$ 10.0 d). In addition to
their longer half-lives, these two isotopes have the potential of
dramatically increasing the therapeutic efficacy of TAT as they each emit
four $\alpha $ particles in their decay chain. This principle has recently
been exploited in the development of Xofigo$^{\mathrm{\mbox{\textregistered
}}}$, the first TAT agent approved for clinical use by the U.S. FDA. Xofigo,
formulated as $^{\mathrm{223}}$RaCl$_{\mathrm{2}}$, is used for treatment of
metastatic bone cancer in men with castration-resistant prostate cancer. TAT
with $^{\mathrm{223}}$Ra works, however, only in the case of bone cancer
because radium, as a chemical analogue of calcium, efficiently targets bone.
In order to bring the benefits of TAT with $^{\mathrm{223}}$Ra or
$^{\mathrm{225}}$Ac to other tumor types, a new delivery method must be
devised. Retaining the \textit{in vivo} $\alpha $ generator radionuclides at the target site
through the decay process is one of the major challenges associated with the
development of TAT. Because the recoil energy of the daughter radionuclides
from the $\alpha $-emission is $\sim$ 100 keV -- a value which is
four orders of magnitude greater than the energy of a covalent bond - the
daughters will not remain bound to the bioconjugate at the targeting site.
Various approaches have been attempted to achieve retention of the $\alpha
$-generator daughter radionuclides at the target site, including
incorporation of the \textit{in vivo} generator into liposomes and fullerenes.
Unfortunately, to date single wall liposomes and fullerenes are able to
retain less than 10{\%} of the daughter radionuclides. We have recently
demonstrated that a multilayered nanoparticle-antibody conjugate can deliver
multiple $\alpha $ radiations from the \textit{in vivo }$\alpha $-generator
$^{\mathrm{225}}$Ac at biologically relevant receptor sites. The
nanoparticles retained over 90{\%} of the $^{\mathrm{221}}$Fr daughter over
the course of three weeks in \textit{in vitro} experiments. In \textit{in vivo} experiments, approximately
90{\%} of the $^{\mathrm{213}}$Bi was retained in the target tissue 24 hours
after injection of the antibody labeled nanoparticle. An overview of the
development and application of this promising, new approach to targeted
alpha therapy will be presented.
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2014.APR.H3.1