EANM’06 – CME Session XIII
October 4, 2006, 10:00 – 11:30
New emerging applications in radionuclide therapy: from basics to bedside
Moderator: B. Brans (Heerlen)
Co-Moderator: C. A. Hoefnagel (Amsterdam)
|P. Blaeuenstein (Zurich):
New therapeutic radioisotopes
|U. Haberkorn (Heidelberg):
New molecular targets for radionuclide therapy
|S.-E. Strand (Lund):
New dosimetric methods
Upon completion of this course the attendee will:
- know the physical properties of some newer therapeutic radionuclides, such as 213Bi, 212Pb 177Lu, 166Ho or 67Cu, and how these can be optimized in relation to the pharmaceutical compound and the tissue to be targeted;
- understand the requirements for specific and effective labelling of these therapeutic radionuclides, including means of production and costs;
- know a number of new targets for radionuclide therapy that can be defined today;
- understand what is needed for their development and how they are tested in preclinical models;
- understand variations of radiation dose distribution within organs and tumors, for example as a result of heterogeneity of activity distribution;
- know the basis of cellular dosimetry and be able to discuss uncertainties in internal dosimetry.
Radionuclide therapy is characterised by selective delivery of radiation doses to target tissues and by limited immediate and long-term side effects in comparison to other treatment modalities, e.g. chemotherapy and external beam radiotherapy. Moreover, experience with radioimmunotherapy for non-Hodgkin lymphoma has shown that the radiolabeled equivalent, the “hot” antibody, can be more effective than the unlabeled, “cold” one.
The proliferation of cyclotrons, primarily for the production of positron-emitting isotopes, implies an opportunity to extend the development of new therapeutic radionuclides, especially those intended to have advantages over the “older”, available therapeutics. Examples may be the short-ranged isotope Lutetium, optimized to target small tumors but with fewer radioprotection issues than 131I, or alpha-emitters such as 211At, that may quantitatively highly increase dose delivery.
On the other part of the radiopharmaceutical, the huge developments in molecular medicine and biology techniques make it possible today to rapidly identify and experimentally test new substances such as monoclonal antibodies or fragments, peptides, peptidomimetics, oligonucleotides, amino acids. The target ligands should be carefully chosen, i.e. they should be overexpressed on the target cells, easily accessible for ligand delivery, not be shed or downregulated. Internalisation of the radiopharmaceutical (or part of it) and cellular blocking without wash-out may be additional important properties.
In all radiation therapy it has been the aim to physically measure delivered radiation dose, and this preferentially before therapy, to allow dose individualization and escalation. This is also the case for radionuclide therapy. It has become clear that clinical calculation is importantly influenced by heterogeneity of radiopharmaceutical delivery and hence activity/dose distribution at a cellular level. To minimize the clinical effects of these errors, one way is to make uncertainty calculations to target tissue as well as normal organs to assist in optimal activity administration choices. Cellular dosimetry is a new concept to account for the microscopic variations. Different methods may be implicated to obtain information on the activity content in organs, tissues and cells, including PET-scan techniques and invasive tissue sampling.
The goals of this CME Radionuclide Therapy/Dosimetry is to inform physicians, physicists, radiochemists, radiopharmacists and others about these new emerging techniques and applications that are likely to have an impact on medical practice in the coming years.
Radionuclide therapy, Therapeutic radio-isotopes, Molecular radiotherapy, Radiation dose distribution, Cellular dosimetry