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JOINT RESEARCH CENTRE - Work Programme 2012
Action n° 51502 - AIT - Alpha-Immunotherapy
Institute for Transuranium Elements (Karlsruhe/Ispra)
Thematic Area:
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TA5 Nuclear safety and security
Policy Theme: 5 - The EURATOM programme
Agenda No & Title: 5.1 - Nuclear waste management and environmental impact
Sub-agenda No & Title: 5.1.5 - Medical applications from nuclear research
Type:: Action
Action Leader: MORGENSTERN Alfred JRC.E.5
External Customer and Stakeholder:
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Albert Einstein College of Medicine
ALBERTLUDWIGSUNIVERSITAET FREIBURG
ERASMUS MEDICAL CENTER ROTTERDAM
Institut de recherches subatomiques
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
JOHANNES GUTENBERG UNIVERSITAET MAINZ
Medical University of Warsaw
Radiochemistry Department (Delft University of Technology)
ST GEORGE'S HOSPITAL MEDICAL SCHOOL
Technische Universität München
UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
University of Gothenburg
University of Ljubljana
Johns Hopkins School of Medicine
Paul Scherrer Institute
Rutgers University
University Hospital Heidelberg
Customer DGs (inside the European Commission):
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RTD - Research and Innovation
SANCO - Health and Consumers
Keywords:
Health, cancer therapy, infectious diseases, alpha emitters, radionuclide generators,
production methods, chelate molecules, radiobiology, pre-clinical testing, clinical study,
training, radiation protection
Rationale:
Radionuclides are used in medicine for the diagnosis and treatment of various diseases,
including some of the most frequent ones, like cancers, cardiovascular and brain diseases.
Over 10000 hospitals worldwide use radioisotopes for the in vivo diagnosis or treatment
of about 35 million patients every year, of which 9 million in Europe.
In its communication on medical applications of ionizing radiation and security of supply
of radioisotopes for nuclear medicine to the European Parliament and the Council
(SEC(2010) 974), the European Commission has identified key challenges in the field of
nuclear medicine, in particular securing supply of radioisotopes for nuclear medicine and
improving radiation protection of patients and staff.
Subsequently, in its conclusions "Towards the Secure Supply of Radioisotopes for
Medical Use in the European Union" the Council of the European Union has stressed the
need for continued efforts to actively investigate economically feasible alternatives to the
current radioisotope production methods and the isotopes currently used.
To address these challenges, the Alpha-immunotherapy (AIT) action at JRC-ITU is
developing methods for the production of established as well as alternative radionuclides,
and is studying their application for the treatment of cancer and infectious diseases as
well as providing training to hospital staff on safe handling of alpha emitting
radionuclides in hospital settings.
The action is particularly focusing on the investigation of radionuclides emitting alpha
radiation, in an approach called Targeted Alpha Therapy - TAT. TAT is taking advantage
of the unique physical properties of alpha radiation, in particular its high energy and short
path length in human tissue, to selectively address and destroy diseased cells while
sparing surrounding healthy tissue and minimizing toxic side effects.
JRC-ITU is presently the only facility within the European Union capable of producing
the alpha emitters Actinium-225 and Bismuth-213 in clinically relevant levels. Due to
ITU's unique facilities, the development of methods for the production of clinical grade
alpha emitters, the synthesis of radioconjugates and their radiobiological testing in vitro
are core competences of the action. Pre-clinical in vivo studies and patient trials are
conducted in collaboration with hospitals and cancer research centres in Europe, USA
and Australia.
Summary of the project:
The action will continue to contribute to all stages of the development of targeted alpha
therapy from bench to bedside to support its clinical implementation for the treatment of
cancer and infectious diseases.
The development and optimization of radionuclide generators for the production of the
alpha emitters in clinical settings will be a core activity together with the development of
improved radionuclide production methods.
Chelate molecules suitable for the stable binding of alpha emitters, e.g. uranium-230 to
biomolecules will be synthesized and tested and protocols for the synthesis of
radioconjugates will be developed. The characterisation and radiobiological testing of
novel radioconjugates in vitro will focus on glioblastoma and glioblastoma stem cells to
improve strategies for the treatment of brain tumors.
In vivo pre-clinical studies and clinical trials will be performed in collaboration with
partner hospitals. Here a main focus will be on clinical trials of peptide receptor
radiotherapy for the treatment of neuroendocrine and brain tumors.
Efforts will be continued to improve radiation protection in clinical settings through
provision of training courses and development of automated systems to reduce radiation
exposure to medical staff.
Specific Objectives for 2012:
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Objective 1:
Development of methods for the production of radionuclides for clinical
application
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Deliverable 1.1: 2012-12-31 00:00:00.0. Development and
performance testing of high activity (> 50 mCi) Ac-225/Bi-213
radionuclide generators for clinical application
[JRC Scientific Support - Technical systems]
Deliverable 1.2: 2012-12-31 00:00:00.0. Development of methods
for the production of uranium-230 and thorium-226
[Scientific Publications]
Objective 2:
Development of chelate molecules and labeling protocols for the synthesis of
radioconjugates for clinical application
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Deliverable 2.1: 2012-12-31 00:00:00.0. Development of methods
for the synthesis of actinium-225 labeled peptides for application
in peptide receptor therapy of cancer
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[JRC Scientific Support - Validated methods, Reference methods
and measurements]
Deliverable 2.2: 2012-12-31 00:00:00.0. Synthesis and
characterisation of molecules for the binding of uranium-230 to
biomolecules
[JRC Scientific Support - Technical systems]
Objective 3:
In vitro and in vivo evaluation of radioconjugates labeled with alpha emitters
to study their potential for application in cancer therapy
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Deliverable 3.1: 2012-12-31 00:00:00.0. Description of the
cytotoxicity of radioconjugates labeled with Bi-213 or Ac-225
towards glioblastoma cells and glioblastoma stem cells.
Description of the stability and binding affinity of uranium-230
labeled biomolecules and their cytotoxicity towards cancer cells.
[Scientific Publications]
Deliverable 3.2: 2012-12-31 00:00:00.0. In vivo evaluation of
radioconjugates for the treatment of neuroendocrine tumors, breast
cancer and bladder cancer as well as infectious diseases in
collaboration with external partners.
[Scientific Publications]
Objective 4:
Clinical testing of peptides labeled with Ac-225 or Bi-213 for the treatment of
neuroendocrine tumors and brain tumors
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Objective 5:
Deliverable 4.1: 2012-12-31 00:00:00.0. Accrual of clinical data
on the toxicity and therapeutic efficacy of Bi-213 or Ac-225
labeled DOTATOC for the treatment of neuroendocrine tumors
[Scientific Publications]
Deliverable 4.2: 2012-12-31 00:00:00.0. Accrual of patient data
on the toxicity and therapeutic efficacy of Bi-213-SubstanceP for
the treatment of brain tumors
[Scientific Publications]
To improve the radiation protection of medical staff during clinical
application of radionuclides
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Deliverable 5.1: 2012-12-31 00:00:00.0. To provide training to
hospital personnel for the safe use of radionuclide generators and
alpha emitting radionuclides in clinical settings
[JRC Scientific Support - Training]
Deliverable 5.2: 2012-12-31 00:00:00.0. To develop automated
systems for the synthesis of radiopharmaceuticals labeled with
alpha emitting radionuclides to reduce the radiation exposure of
medical staff
[JRC Scientific Support - Technical systems]
Last Updated 08/12/2011 10:36:49