Human Health

Excerpt from the IAEA Annual Report for 1994

(Editor's note: The format of scientific notations in this electronic presentation is being standardized.)


Programme overview

The Agency's programme on human health for 1994 continued to focus on initiatives launched in 1991. However, there has been a gradual transition from a technically oriented programme to one that is medically guided, where the major objective is not the simple transfer of technology but the effort to make it readily available to effectively solve clinical problems. In accordance with this new policy, the highest priorities were given to the curative and palliative treatment of cancer, the detection of diseases prevalent in children and the assessment of nutritional status and the planning and evaluation of applied nutritional programmes for women and children.

Research activities carried out by the Agency received special mention at the 6th Congress of the World Federation of Nuclear Medicine and Biology, held in Sydney, as a model for education, training and research. A CRP on immunoscintigraphy of colonic cancer, which was completed during the year, pioneered the use of monoclonal antibodies labelled with 99Tcm. Other CRPs were designed as randomized multicentre clinical trials for monomodal and multimodal therapeutic approaches, using either open (nuclear medicine) or sealed (radiation therapy) radioactive sources in the treatment of diseases, including hyper-thyroidism and different types of cancer. The aims are to define scientifically in well selected patient populations the best treatment protocols for each type of disease for worldwide application. A new approach was also introduced to increase efficiency in CRPs dealing with advanced technology in nutritional studies by twinning institutes in developed countries with institutes in developing ones. The techniques developed in previous CRPs on the detection of communicable diseases using radioactive nucleic acid probes and the polymerase chain reaction can now be transferred from biological research institutes to clinical practice in hospitals.

Successful completion of previous CRPs on the indigenous production of reagents for radioimmunoassay (RIA) has allowed the start of regional and national programmes for the detection of neonatal hypothyroidism, a major cause of mental and physical deficiency in the world. Similarly, ongoing CRPs on the indigenous production of radioimmunoanalytic reagents for the detection of hepatitis B will provide the springboard for future programmes dealing with this disease of increasing prevalence in the developing world and closely linked to the aetiology of cancer of the liver.

The model project criteria seem to be especially suited for the medical field, as shown by the successful implementation of national projects for nuclear medicine development initiated in Bolivia and other countries since 1992. During 1994, five model projects on human health were approved, dealing with nuclear medicine, radiation oncology, nutritional studies and radiation sterilization of tissue grafts for reconstructive surgery.

As radiation therapy is only curative during the earlier stages of cancer, a collaborative agreement was reached with WHO by which the Agency would give higher priority to radiotherapy projects in which WHO already sustains national programmes for the prevention and early diagnosis of cancer.

As result of the Agency's mediation, some commercial firms began in 1994 the production of simple, low cost gamma cameras and radiation therapy machines with updated technology. These will reduce the cost of technical co-operation projects in the medical field and will enable developing Member States to have better access to equipment. The gamma cameras can be upgraded at minimal cost to digital data and image processing by using the hardware interface and the processing software which have been developed by the Agency and are presently undergoing field trials at selected centres.

The principal emphasis in the field of dosimetry was placed on starting quality assurance (QA) programmes. In co-operation with the European Union, a pilot study for quality control is now being carried out at European radiotherapy centres. In order to improve the calibration of irradiation beams, this programme also includes the examination of all dosimetric steps from dose prescription to dose delivery. Similar QA programmes are being organized for radiotherapy centres in developing countries. A QA programme has been also established for high dose dosimetry.

A CRP on therapy level dosimetry with the alanine/ESR system was terminated in 1993 on the recommendation of the SSDL Scientific Committee since the majority of the participants had changed their priorities and were slow in developing this dosimetry system. The termination data of a CRP on development of quality control dosimetry techniques for particle beam radiation processing was postponed to 1995 because of the deferment of a Research Co-ordination meeting as a result of financial restrictions.

Emphasis in the human nutrition programme continued to be placed on persistent nutrition problems in which nuclear and related techniques can provide critically needed information to improve the efficacy of interventions. To increase the impact on end-user populations, closer collaboration was established with expert groups associated with other relevant international organizations (WHO, UNU, International Union of Nutritional Sciences). Human health related environmental studies have continued to place emphasis on environmental pollution using nuclear and isotopic techniques and on the monitoring of accidentally released radionuclides in environmental and food samples.

The IAEA-MEL continued to act as an experimental focal point for interagency co-operation on marine pollution monitoring, in particular with UNEP and the IOC of UNESCO. It provided training and capacity building related to the implementation of the recommendations of UNCED, Chapter 17, Agenda 21 and it continued therefore to organize training courses, in-service training, Analytical Quality Control Service (AQCS) support to 235 laboratories worldwide, issuance of reference methods for marine pollution studies, equipping of laboratories and the carrying out of pilot monitoring studies. Significant new techniques were added to the Laboratorys analytical capability. Important results in 1994 included the observations that marine corals can record past contamination by oil and that pesticide behaviour in coastal waters is largely controlled by interactions with organic humic compounds.


NUCLEAR MEDICINE

Enhancing the capabilities of developing countries to perform dynamic functional studies

Two CRPs aimed at enhancing capabilities to perform brain and heart function studies have yielded interesting results. Apart from studying diseases of the brain and heart which are common to all parts of the world, attention is being given to disease conditions and treatment practices relevant to developing Member States. Two examples are objective documentation of regional brain blood flow changes following acupuncture and the use of indigenously manufactured drugs to induce pharmacological stress in heart studies.

Screening for neonatal hypothyroidism

A CRP in the Latin American region, aimed at introducing filter paper based RIA of thyroid related hormones using bulk reagents, was concluded. Institutions participating in the CRP were able to absorb this simple and robust technology and use it for large scale screening programmes in a cost effective manner.

Diagnosis of communicable diseases

There were promising developments in CRPs on molecular diagnostics. Results from a CRP on tuberculosis have shown the potential of molecular methods in the early diagnosis of tuberculous meningitis, a condition which is especially difficult to diagnose and which could lead to irreversible neurological damage if specific treatment is delayed. A CRP on blood borne diseases has led to the development of kits for Chagas' disease and leishmaniasis.


APPLIED RADIATION BIOLOGY AND RADIOTHERAPY

Radiation sterilization of medical supplies

A model tissue banking project was initiated in Sri Lanka. Large scale production has begun of clinical quality radiation sterilized tissue grafts, such as bones, skin, fascia lata, duramater and chorion-amnion.

Advanced techniques in brachytherapy

Progress in the development of after-loading techniques, which effectively eliminate the exposure of staff to radiation, has resulted in a general resurgence of interest and an increasing role for brachytherapy in cancer management. Further impetus has been given by the availability of inexpensive PC based treatment planning systems which have been implemented through a recently concluded CRP in the countries of the Asia and Pacific region. Another CRP, on brachytherapy in combination with other methods for the treatment of malignant neoplasia at various anatomical sites, is continuing to provide the potential for introducing high dose rate brachytherapy techniques. The projected activities continue to encourage an evolution towards optimal QA through adherence to basic clinical standards and collimated instruments, as well as proper techniques, dosimetry and reporting systems in clinical brachytherapy.

In order to help developing countries to start or upgrade radiotherapy facilities, projects have been implemented through technical co-operation programmes. Model projects in Ghana and Mongolia are currently in the early implementation phase. Expert missions to Bangladesh, the Dominican Republic and Jordan were carried out to assess current facilities and needs for training radiotherapists and medical physicists.

Comparative assessment of mutagenic and carcinogenic effects of low level radiation and toxic chemicals released from energy cycles

Research on the mechanisms involved in mutagenic and carcinogenic effects from exposure to low level radiation and to genotoxic chemical pollutants has continued in a CRP on radiological methods in comparing the health impacts of radiation and conventional techniques. The work has been facilitated through the provision and validation of current molecular radiobiology techniques, along with the rapid accumulation of data on chemical mutagenesis and carcinogenesis. The nuclear methodologies suitable for quantitative evaluation of mutagenic and carcinogenic effects could thus serve as a basis for a comparative assessment of the potential risk to human health posed by chemical pollutant emissions from fossil fuel energy sources.

Exploration of the stimulative effects of low dose radiation

Results confirming the existence of adaptive response to low dose radiation were generated through a CRP which was completed in 1994. Some of the molecular mechanisms involved relate to the stimulation of cellular repair capacity for damage to the genetic material and also for the enzymatic systems. The findings are expected to have an impact on the interpretations of low dose radiobiological effects and, on particular, on attendant risk assessment.

Development of criteria for tumour responsiveness to radiation for use in treatment planning

Radiobiology data on the radiosensitivity of human tumours generated through a CRP have illustrated that predictive assays can be utilized in radiotherapy treatment planning with the concomitant prospect of enhancing cancer cure rates. Both the intrinsic radiosensitivity of a tumour and its growth kinetic parameters play a role in tumour radioresponse and are hence recommended for use in predicting the outcome of radiation therapy and in the development of an overall superior clinical strategy in cancer management.


DOSIMETRY

Secondary Standard Dosimetry Laboratory (SSDL) network

The IAEA/WHO network of SSDLs presently includes 69 laboratories and 6 SSDL national organizations in 56 Member States, as well as 14 affiliated members (i.e. Primary Standard Dosimetry Laboratories (PSDLs)). The support of the member laboratories has continued. Calibration of 14 secondary standard dosimeters was provided through the Agency's Laboratory at Seibersdorf. The annual dose intercomparisons with SSDLs were extended to medical accelerator beams in addition to the radiation beams of 60Co radiation therapy units. Four SSDLs had a larger deviation than the established acceptance limit of 3.5%. In a repeat of the exercise, three of these four SSDLs corrected their deviations.

Dose intercomparison and assurance

The IAEA/WHO Thermoluminescence Dosimetry (TLD) service was continued for nearly 300 radiotherapy centres in developing countries, checking the calibrations of photon radiation beams from 60Co radiotherapy units and medical accelerators used for patient treatment. About one third of the results were beyond the 5% acceptance limit. In the follow-up measurements, 30% of the participants again showed a deviation above the acceptance limit.

Two TLD dose intercomparison runs with 12 radiotherapy centres in Europe and the USA were implemented for electron beams from medical accelerators. The results provided baseline data for energy correction factors needed to expand the IAEA/WHO TLD service for electron irradiation beams. This additional service is presently being tested with 36 radiotherapy centres in Europe and the USA before it enters into routine operation for hospitals in developing countries.

All TLD intercomparison runs received support from the International Bureau of Weights and Measures (BIPM), the Austrian Primary Standard Dosimetry Laboratory (BEV) or the Radiation Physics Department of the University of Umeaa, Sweden. They provided reference irradiations for all TLD runs as an external quality control measure for the TLD dosimetry service. The BIPM calibrated two therapy level secondary standard dosimeters of the Agency providing traceability to the international measurement system.

The International Dose Assurance Service (IDAS) for high dose dosimetry in radiation processing facilities was continued. A complete QA programme has now been established. The alanine/ESR dosimetry system was calibrated by the National Physical Laboratory, the PSDL in the United Kingdom providing traceability to the international measurement system for high dose measurements. A total of 46 alanine dosimeter sets were distributed to 12 participating institutes from 11 Member States.

An intercomparison for gamma ray irradiation beams between nine calibration laboratories (six out of the nine are primary laboratories), organized in collaboration with BIPM, was started. The last such intercomparison was held about ten years ago.

Laboratory activities

The Dosimetry Unit of the Agency's Laboratory at Seibersdorf continued to provide dosimetric measurement support. It functions as the Central Laboratory of the IAEA/WHO network of SSDLs. In addition, it operates two routine services: the IAEA/WHO TLD service and the worldwide IDAS.


NUTRITIONAL AND HEALTH RELATED ENVIRONMENTAL STUDIES

Applied research on environmental pollution using nuclear and isotopic techniques

Work continued on studies of air pollution using nuclear related analytical techniques. Experience gained from a global CRP on this subject was used to help develop similar activities within the framework of a joint UNDP/RCA/IAEA project on the use of isotopes and radiation to strengthen technology and support environmentally sustainable development. Arrangements were made to supply 15 countries in the Asia and Pacific region with a standard air sampler for the collection of airborne particulate matter, and intercomparison exercises were initiated with three kinds of analytical quality control material.

Progress was achieved in a CRP on the assessment of environmental exposure to mercury in selected human populations as studied by monitoring the concentrations of total mercury and methylmercury in human hair. Mercury has long been known to be a toxic element, but only rather recently has it been recognized that it may have toxic effects on the nervous systems of newborn babies, even at very low concentrations. At the third Research Co-ordination Meeting, held in Monaco, data were presented on total mercury and methylmercury in human hair, emphasizing data for pregnant women and their newborn babies. Through this CRP a network of laboratories has now been established that can reliably determine mercury and methylmercury in hair samples. An intercomparison on total mercury, methylmercury and other trace elements in two human hair materials (IAEA-085/086) was organized in 1994.

Services to international marine pollution monitoring programmes

Quality assurance work within the AQCS programme continued and a mussel homogenate sample (IAEA-142) was distributed worldwide to 235 laboratories for intercomparison of organic contaminants. In addition, 15 expert laboratories were invited to measure methylmercury compounds for subsequent certification purposes. Work commenced on the preparation of a new intercomparison sample called IAEA-140, Sea Plant Homogenate. This material will be distributed to over 400 laboratories worldwide for the analysis of organic contaminants, trace elements and methylmercury.

A report on the worldwide and regional intercomparison for the determination of trace elements and methylmercury compounds in polluted marine sediment, IAEA-356, was completed. In total, 68 laboratories from 41 countries reported results for up to 61 elements. Methylmercury was also certified and this represents the first sediment sample ever certified for this very toxic organomercury compound. The IAEA-356 sample can now be considered as a reference material.

In co-operation with the IOC of UNESCO, IAEA-MEL has been active in the International Mussel Watch project, which was set up to assess the global distribution and investigate the transport of persistent organochlorine pollutants. Mussel samples taken from Central and South America were analysed. Results identify some hot spots, but a comparison with data for the USA issued by the National Oceanic and Atmospheric Administration shows that contamination is generally lower than in North America.

The IAEA-MEL continued to assist the Regional Organization for the Protection of the Marine Environment (ROPME) in Kuwait in obtaining information on the spatial and temporal distribution of marine contaminants in various locations in the Persian Gulf. During 1994, two new projects were established between IAEA-MEL and ROPME. One project on QA for contaminant measurements involves co-ordinating intercomparison exercises and training activities in the region. The second deals with a thorough screening for key contaminants in the northern waters of the Persian Gulf.

During 1994, a new research activity was introduced on the use of corals as historical recorders of pollution. The tissues of corals deposit an exoskeleton beneath their outer living film at a rate dependent on growth and hence on environmental conditions. This typically results in annual (seasonal) bands being formed within colonies. Recent results suggest that coral skeletons record contamination from oil and could potentially be used to investigate other anthropogenic and biogenic organic inputs. Analyses of sections from within corals sampled from the coasts of Kuwait and Saudi Arabia demonstrate discrete bands of oil contamination which, using selected terpenoid biomarkers, can be source indexed to specific oil fields. Together with dating using microscopic and X ray inspection, this offers the opportunity precisely to investigate contamination during recent years.

Work continued on the development and testing of new methodologies for the quantification of organometallic compounds and achievements in this field led to the IAEA-MEL being selected as a Reference Laboratory in the first international intercomparison exercise for the determination of organomercury compounds in natural water samples.

Mechanisms controlling the cycling and fate of pesticides in the marine environment were studied under controlled laboratory conditions using 14C labelled organochlorine and organophosphorus compounds. It was found that the partitioning of these pesticides between water and sediments is largely controlled by their interaction with organic matter such as humic substances.

Laboratory activities

The R&D work at the Agency's Laboratory at Seibersdorf focused mainly on environmental pollution studies using nuclear and isotopic techniques for investigations of environmental exposure to mercury and in air pollution research. In the latter project, the laboratory joined efforts on the evaluation and use of PM10 air particulate matter samplers and related analytical work. A collection of 24 h samples was carried out in Vienna, and analytical results have been obtained by proton induced X ray emission (PIXE), instrumental neutron activation analysis (INAA) and atomic absorption spectroscopy (AAS). In support of such measurements, new intercomparison and reference materials for air pollution studies are being developed. A set of relevant samples, urban dust, soil dust and coal fly ash, were prepared and distributed to the RCA participant group on nuclear analytical techniques.

Services related to the development and selection of analytical techniques and procedures for the monitoring of accidentally released radionuclides into the environment included the implementation of a new rapid chromatographic separation in the 90Sr procedure. Simultaneously, low level gamma spectrometry procedures were developed and established. The increased sensitivity is utilized in studies relating to the assessment of effluents from nuclear operations (and also for safeguards purposes) and residues at former weapons test sites (Kazakhstan).

Two milk powder quality control materials for radionuclides (with different levels of 134Cs, 137Cs and 40K) were provided by the AQCS for a collaborative study with the WHO Regional Office for Europe to evaluate laboratory proficiency.