Molecularly Targeted Radiation Therapy: Towards Individualised Treatment
1CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK
Molecularly targeted radiation therapy combines the cytotoxicity of ionizing radiation with the targeting potential of molecular therapeutics and so enables individualised treatment. Recent clinically important advances in the field include the introduction of Ra-223 for the treatment of metastatic prostate cancer and the emergence of selective internal radiation therapy (SIRT) as an effective treatment for hepatic metastases.
The ionizing emissions from radionuclides used in cancer treatment include short-range electrons such as Auger and interval conversion electrons, beta electrons and alpha particles as well as gamma photons. Many factors contribute to the extent and pattern of radiation dose deposition following administration of radionuclide-based treatments. These include the physical properties of the radionuclide itself as well as the pharmacokinetics and the biodistribution at the whole body and organ level of the carrier molecule to which the radionuclide is conjugated. In some cases the extent of cellular uptake and intracellular distribution of radioactivity also determines the fate of targeted cancer cells. These complexities have hampered progress towards individualized treatment plans and rendered the development of rationale protocols for combining radionuclide therapy with external beam radiation therapy challenging. Many new radiopharmaceuticals are designed as theranostic agents, with dual imaging and therapeutic roles. A detailed understanding of the biodistribution and biological consequences of administration of radionuclides used in PET and SPECT probes is therefore also important.
We have developed new autoradiographic methods for detection of radionuclides in individual cells and 3D multicellular models at the nanometer to micrometer scale and have used Monte Carlo simulation to illuminate the biological consequences of differences in distribution. In this session the application of these methods to peptide-, antibody, and nano- and micro-particle based radiopharmaceuticals will be discussed.