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Requirements for acquiring dosimetry in clinical trials with therapeutic radiopharmaceuticals.

Cremonesi M.
  Mercoledì 28/09   10:00 - 13:00   Edificio Psicologia 2 - Aula 2C   V - Biofisica e Fisica medica
In recent years, radionuclide therapy has shown an increasing variety of applications that follows the availability of new receptor ligands, monoclonal antibodies, metabolic precursors, and innovative devices. Moreover, a variety of radionuclides, emitting nuclear particles with very different path lengths (nanometers to millimeters), and clinical strategies are currently used, for which different organs are at risk. As a natural consequence, clinical trials for new applications have been increasing, for which dosimetry is required. The main challenge is to determine dose-response relationships, but even the identification of the organs at risk and the basic evaluation of the radiation dose to tumors and normal tissues can be of primary importance. In fact, there is the need to characterize the radionuclide therapy, to prove safety, and, not least, to certify the pertinence of the research methodology, having explored any possibility to prevent unwanted radiation effects. Contrarily to the majority of diagnostic applications, in the therapeutical field serious radiation-induced deterministic effects can occur, so, in a phase-I clinical trial safety is evaluated and a safe dosage range is determined. In most cases a well-performed dosimetric study is crucial, for the future use of the specific radiopharmaceutical/device. Wide intra-patient variability is typically found, so patient-specific dosimetry is necessary for tailored radionuclide therapies. Activity-based dosage ranges tend to lead to under-treatment of most patients as they are based on the response of the most sensitive patient cohort. The main aim of this presentation is to summarize the various aspects that should be considered for dosimetry investigation in clinical trials. There are many facets that are to be included, such as: organizational issues; selection of the appropriate radiopharmaceutical to evaluate dosimetry for difficult-to-quantify radionuclides; equipment selection and calibration; identification of dataset collection for pharmacokinetics and imaging (planar 2D, 3D SPECT, PET); methods for data processing. Concrete examples of dosimetric protocols will be regarded in detail for various radionuclide therapies, with particular focus on ${}^{177}Lu$-peptide receptor radionuclide therapy addressed to neuroendocrine tumors and radioembolization of liver lesions with ${}^{90}Y$-microspheres.