Yttrium-90 and Rhenium-188 Radiopharmaceuticals for Radionuclide Therapy

FOREWORD
The IAEA helps to promote and support the development of new, more
effective approaches to cancer treatment. Radionuclide therapy is a versatile
nuclear medicine application using ionizing radiation for the treatment of various
degenerative diseases including cancer. In contrast to radiation therapeutic methods,
which use an external ion beam source, internal radionuclide therapy is performed
by the intravenous administration of radionuclides conjugated to a molecular
substrate. In contrast to chemotherapy, radionuclide therapy requires very low
mass amounts of the targeting compound. The therapeutic effect is achieved by the
ionizing radiation of the radionuclide and not by the pharmacological effect of the
carrier molecule. The therapeutically effective radiation dose is determined by the
physical characteristics of the radionuclide. Results show that radionuclides with
long range beta emission, such as 188 Re and 90 Y, are the most efficient agents for
irradiation of larger tumours.
Another advantage of radionuclide therapy compared with other types of
cancer therapy is the possibility to determine selective accumulation in the targeted
tissue by imaging using single photon computed tomography or positron emission
tomography after the injection of diagnostic compounds that are structurally
identical to the therapeutic counterpart. These non-invasive imaging methods
also allow dose calculation prior to therapy, staging and monitoring of therapeutic
efficacy.
The success of radionuclide therapy depends not only on the selection of an
appropriate radionuclide but also on the pharmacodynamic and pharmacokinetic
properties of the radiolabelled targeting vehicle. As the most sensitive non-invasive
modality currently available for the detection and mapping of disease specific
biomarkers, nuclear medicine plays a strategic role at the forefront of this trend.
Many of these biomarkers or their natural ligands can be translated into potential
imaging agents. These agents can be used to demonstrate the presence of appropriate
molecular targets, or, when labelled with beta or gamma emitting radionuclides,
will also be suitable for targeted radiotherapy.
Following a coordinated research project (CRP) focused on therapeutic
radiopharmaceuticals, a CRP titled Development of Radiopharmaceuticals based on
188 Re and 90 Y for Radionuclide Therapy was initiated, aimed at stimulating research
on the use of these two high energy beta emitters for developing new therapeutic
radiopharmaceuticals. Emphasis was also given to the development of reliable and
efficient quality control methods for determination of the radionuclidic purity of the
radionuclide solutions employed in the production of the final therapeutic agents.
Results of these investigations and some important experimental protocols are
described in this report, which also includes a general introduction to the principles
and concepts of radionuclide therapy.