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RELATION BETWEEN DECORPORATION OF OSTEOTROPIC ALPHA EMITTERS AND LONG TERM PREVENTION OF RADIATION HARM

Objetivo

THE PROPOSAL AIMS AT ELUCIDATING TWO MAIN PROBLEMS:
1) WHY IS A SUBSTANTIAL DECREASE OF BODY-BURDEN BY DECORPORATION TREATMENTS (SUCH AS WAS OBTAINED WITH RA-226 IN MICE) NOT REFLECTED IN A DECREASE OF BONE CANCERS? IS THIS A GENERAL PHENOMENON, OR ONLY DUE TO SOME SPECIFIC PROPERTIES OF RA-226?
2) CAN A SUBSTANTIAL IMPROVEMENT IN DECORPORATION OF RADIOACTIVE HEAVY ALKALINE EARTH METALS BE OBTAINED BY CHANGING THE FIRST SUCCESSFUL APPROACH OF TREATMENT?
The incidence of osteosarcoma in mice has been studied in terms of its dependence on the level of incorporated radionuclides in bone as influenced by decorporation treatment. The initial radium-226 radiation dose to cells at risk determines the late radiation effects. Therefore the time lapse between decorporative treatment and radium-226 radiocontamination should be as short as possible.
SUBPROJECT 1: DECREASE OF LONG-TERM HARM (BONE CANCER INDUCTION) BY DECORPORATION OF OSTEOTROPIC A-EMITTERS.
RESEARCH SPONSORED BY THE FORMER CEC CONTRACT BI0-D-381-B SHOWED THAT A 50% DECREASE OF RA-226 CONTENT DID NOT ALTER SUBSTANTIALLY THE OSTEOSARCOMA INCIDENCE IN MICE.
THE FOLLOWING POINTS ARE PROPOSED TO BE INVESTIGATED:
1) IS THE OBTAINED REDUCTION IN BODY-BURDEN LINKED TO A CHANGE IN MICRO-DISTRIBUTION OF THE REST OF THE ALPHA-EMITTERS IN BONE, BRINGING IT IN CLOSER CONTACT WITH TARGET-CELLS FOR BONE CANCER INDUCTION, AND THUS INCREASING THE CANCER RISK DUE TO THAT PART OF THE BODY-BURDEN?
2) TO WHAT LEVEL MUST THE BODY-BURDEN BE DECREASED BEFORE A PROTECTION AGAINST OSTEOSARCOMA IS OBTAINED?
3) IN HOW FAR IS THE LACK OF LONG-TERM PROTECTION LINKED TO THE CHARACTERISTICS OF THE RADIOISOTOPE; AND CAN SIMILAR LACK OF PROTECTION AFTER DECORPORATION BE PREVENTED FOR OTHER HIGH RISK ISOTOPES SUCH AS AM-241 AN CM-242 (CHOSEN DUE TO THEIR PREDOMINANT ROLE IN AGED NUCLEAR WASTE) OR SR-90 (CHOSEN DUE TO ITS POTENTIAL DANGER IN CONTAMINATION OF LARGE POPULATION GROUPS AFTER A NUCLEAR ACCIDENT)?
THIS RESEARCH WILL HELP TO GUIDE DECORPORATION RESEARCH IN GENERAL, TO MORE SENSEFUL METHODS AND TO A RAPPRAISAL OF THE SHORT-TERM EXPERIMENTS DONE SO FAR.
SUBPROJECT 2: CHRONIC DECORPORATION OF HEAVY ALKALINE EARTH METALS.
THE SUCCESS IN DECORPORATION OF RA-226 COULD BE SUBSTANTIALLY IMPROVED BY APPLYING THE MORE EFFECTIVE AND SOPHISTICATED METHODS OF CHRONIC ADMINISTRATION OF THE SPECIFIC BINDING AGENTS SUCH AS ALGINATES. MOREOVER, THE INFORMATION GAINED ON RA-226 (STILL REMAINING THE BASIC STANDARD FOR ALPHA-EMITTING OSTEOTROPIC ISOTOPES) HAS TO BE EXTENDED TO SR-90 WHICH IS OF MORE PRACTICAL IMPORTANCE FOR RADIOPROTECTION.
IN LONG-TERM EXPERIMENTS, A MORE EFFECTIVE DECORPORATION OF RA-226 (IN A LIMITED EXPERIMENT WITH 80 MICE) BY DAILY MIXED TREATMENT (INJECTION AND FOOD ADDITIVE) WITH THE BINDING AGENTS WILL BE ATTEMPTED. A LARGER EXPERIMENT (400 MICE) WITH SR-90 WILL INVESTIGATE WHETHER PRACTICAL DECORPORATION AND OSTEOSARCOMA PREVENTION IS OBTAINABLE. A COMPARISON WITH A LIMITED AMOUNT OF 80 RATS, HAVING A THICKER SKELETON AND RELATIVELY MORE ABSORPTION OF THE SR-90-BETA RAYS WILL GIVE A FIRST IDEA OF THE RELIABILITY OF EXTRAPOLATION OF THE SO OBTAINED RESULTS.
PART OF THE EXPERIMENTS OF SUBPROJECT 1 AND 2 ARE LINKED; THIS IS MOSTLY TRUE FOR POINT 1 OF SUBPROJECT 1 (CHANGES IN MICRO-DISTRIBUTION) AND SUBPROJECT 2 AS A WHOLE.

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CSC - Cost-sharing contracts

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CENTRE D'ETUDES DE L'ENERGIE NUCLEAIRE
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PARC SENY RUE CHARLES LEMAIRE 1
1160 BRUSSELS
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