CME 2 Session – EANM’13

(1)
PRRT: New Approaches

Educational objectives:
  1. To learn the necessary basic knowledge on the genomics underlying the development and progression of neuroendocrine tumours, as well as their response to therapies
  2. To show the possibilities and limits of a dosimetric approach to PRRT and the potential for radiobiology
  3. To have an overview of the current status of clinical protocols of PRRT in neuroendocrine tumours and the possibility of personalised treatments
Summary:
This continuing education session is directed primarily towards nuclear medicine physicians who are interested in performing PRRT in a comprehensive and modern environment and, hence, to deliver the treatment in a safe and effective manner.
Peptide Receptor Radionuclide Therapy (PRRT) consists of the systemic administration of a synthetic somatostatin analog, radiolabeled with a suitable beta-emitting radionuclide. The compound is able to irradiate tumours and their metastases via internalisation through somatostatin receptors over-expressed on the cell membrane. As a result, the radiopharmaceutical is concentrated in the tumour cell, where sensitive molecules, such as DNA, can be targeted.
In more than 15 years of academic phase I/II trials, despite the lack of homogeneity among studies, PRRT has proved to be efficient and consistent in efficacy and has, ultimately, demonstrated an impact on survival. Side effects of PRRT typically affect the kidneys and the bone marrow. These, however, are mild, provided adequate protective measures are undertaken.
Despite the large body of evidence regarding efficacy and clinical safety of the fixed dose approach, PRRT still has grey zones of inefficient treatments due to the administration of inadequate absorbed doses to the target or excessive absorbed doses to normal organs.
The first lecture of this CME will give an overview on the genomics that sustain the development and progression of neuroendocrine tumours (NET), defining the interactome of neuroendocrine cells and its relevance to the development of (drone) therapy, providing a platform to understand the development of Master regulator genes and their role in identifying druggable addiction points, defining the mutational spectrum of NET tumourigenesis to understand the induction of NET neoplasia, establishing the basis of blood transcript analysis in diagnosis of NET disease and the role of molecular transcripts as a surrogate marker for the efficacy of PRRT.
The second lecture will examine dosimetric and radiobiologic approaches to PRRT with either 90Y or 177Lu radiopeptides as a basis for personalisation of treatment. The advantages and disadvantages of this over a population based approach will be considered and radiobiological aspects of ‘cocktail’
administrations of more than one radiopharmaceutical will be explored. The practicalities of a dosimetric approach to treatment in terms of resource requirements will also be taken into account.
The third lecture will give an overview on the current clinical protocols of PRRT, which are reflected in the common document that has been written by experts reunited under the auspices of IAEA, EANM and SNMMI. The lecture will give an overview on the current advantages and limitations of PRRT, will define the parameters of standardisation that can be regarded as milestones today, and will explore the possibility of going towards personalised treatments, capitalising the input deriving from the biologic and dosimetric approaches.

Key Words:
PRRT, 90Y-Octreotide, 177Lu-Octreotate, Genomic Approach, Radiobiology, Dosimetry

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