Biological carrier molecules of radiopharmaceuticals for molecular cancer imaging and targeted cancer therapy.

Many tumors express one or more proteins that are either absent or hardly present in normal tissues, and which can be targeted by radiopharmaceuticals for either visualization of tumor cells or for targeted therapy. Radiopharmaceuticals can consist of a radionuclide and a carrier molecule that interacts with the tumor target and as such guides the attached radionuclide to the right spot. Radiopharmaceuticals hold great promise for the future of oncology by providing early, precise diagnosis and better, personalized treatment. Most advanced developments with marketed products are based on whole antibodies or antibody fragments as carrier molecules. However, a substantial number of (pre)clinical studies indicate that radiopharmaceuticals based on other carrier molecules, such as peptides, nonimmunoglobulin scaffolds, or nucleic acids may be valuable alternatives. In this review, we discuss the biological molecules that can deliver radionuclide payloads to tumor cells in terms of their structure, the selection procedure, their (pre)clinical status, and advantages or obstacles to their use in a radiopharmaceutical design. We also consider the plethora of molecular targets existing on cancer cells that can be targeted by radiopharmaceuticals, as well as how to select a radionuclide for a given diagnostic or therapeutic product.

Radiological impact of almost a century of phosphate industry in Flanders, Belgium.

In Belgium, since about 1920, the phosphate industry has been an important industrial activity. It is principally situated in Flanders, the northern part of Belgium, and produces mainly phosphoric acid, fertilizers, and cattle food. At its height, between 1980 and 1990, it processed between 1.5 and 2.0 Mt of phosphate ore of varying origin per year. In total, more than 60 Mt of ore were handled, containing about 72 TBq of 226Ra and 3.5 TBq of 232Th. Three different processing techniques in six large production sites gave rise to 50 Mt of phosphogypsum and 2.7 Mt of calcium fluoride sludge, all mainly stored on large deposits. In addition, limited recycling of phosphogypsum as building material has occurred in the past. Also, 10 Mt of phosphogypsum was discharged into a large tidal river. One plant still produces 0.25 Mt of gypsum per year. Liquid effluents, containing 13 TBq of radium chloride, were discharged into two small rivers, thus contaminating over 200 ha of land. Approximately 8 TBq of 226Ra and 0.6 TBq thorium ended up in finished products such as fertilizers. Despite these large production figures, so far the radiological impact for the Flemish population has been limited, but this might worsen in the future. The major risk consists in establishing residential areas on land that is contaminated with 226Ra because of liquid effluents or on forgotten gypsum deposits. Doing so might lead to enhanced indoor radon concentrations. In three isolated cases, we found houses built on gypsum deposits where the increased indoor radon levels raised the annual radiation dose to the inhabitants by about 4 mSv.

Radon: a special case in radiation protection.

The conversion conventions of ICRP 65 are based on equality of detriment, not on dosimetry. They are derived from epidemiological studies on miners by comparing the risk of having fatal lung cancer with the detriment associated with a unit of exposure in ICRP 60. Things have moved on since ICRP 65 and the new scientific evidence (numerator change, denominator change and also the dosimetric approach in ICRP 66) is pointing away from ICRP 65 in the direction of the long-established UNSCEAR conversion factor of 9 (nSv h(-1))/(Bq m(-3)) radon progeny exposure, which is 50% higher than the ICRP 65 conversion convention for members of the public. Anyhow, smoking, by the almost multiplicative relationship with radon, determines to a considerable extent the lung cancer risk. Although there is a fairly general consensus among health physicists that radon exposure constitutes the largest and most variable contribution to the population exposure from natural sources, they are divided between themselves on the numerical value of the risk estimates and on the need and urgency to incite the population to take action. This relaxed attitude to radon exposure is reflected in the regulatory approach, which is very much in line with the perceived risk by the population.

Assessment of radiation exposure in the uranium mining and milling area of Mailuu Suu, Kyrgyzstan.

The area of the town of Mailuu Suu, Kyrgyzstan, is polluted by radionuclides and heavy metals from tailing dumps and heaps resulting from the historic exploitation of uranium mines. In the frame of a European Commission-TACIS funded project, radiological assessment was performed for critical group members living in the city of Mailuu Suu, located downstream the tailings, or in the village of Kara Agach, partially located on a uranium mine waste dump. The actual external exposure is around 1.2 mSv a(-1) at both locations and exposure from radon is around 3 mSv a(-1) at Mailuu Suu and around 10 mSv a(-1) at Kara Agach. Ingestion dose was negligible for a critical group member living at Mailuu Suu. At Kara Agach, however, under the hypothesis that all food and fodder is cultivated locally, exposure from ingestion is much higher ( approximately 10-30 mSv a(-1)). In case of an accidental scenario [(part of) Tailing 3 content thrust to river], estimated additional maximum doses result in 45 and 77 mSv for an adult and a child, respectively.

The radiological impact from airborne routine discharges of a modern coal-fired power plant.

In this paper the radiological impact from the airborne routine discharges of a modern coal-fired power plant at Langerlo (Belgium) is evaluated. Therefore, the natural radioactivity contents of the coal and the fly-ash discharged were measured. With a bi-Gaussian plume model the maximum annual values of the 226Ra concentration in the air (4.5 nBq/m3) and of the total deposition (1.5 mBq/m2) were calculated. The transfer of the radionuclides from air and soil to the biospheric media, exposing man, were modelled and the annual, individual, effective dose to the critical group, after an assumed life span of the power plant of 70 years, was evaluated at 0.05 microSv/y. This is several orders of magnitude lower than the annual doses for most power plants reported in the literature. The flue gas purification system, extended with a denitrification unit and a desulphurisation unit, was found to be the basis for this low impact.

Radium contamination of the banks of the river Laak as a consequence of the phosphate industry in Belgium.

For over half a century, phosphate ores of marine origin, containing 226Ra, have been processed in Belgium to produce calcium phosphate for use in cattle food. As a result, the waste water containing 226Ra were discharged into two little rivers, one of which is the Laak. The purpose of this study was to chart the radium contamination of the river banks and some areas that are regularly flooded by the river. It was seen that enhanced concentrations of 226Ra do occur along the river banks, but that the contaminated area is mostly confined to a 10 m strip on both sides of the river, even in the flooding zones. At present, no dwellings are present on top of the contamination and no crops for direct human consumption are grown there, so there is no immediate threat to the population.

Retrospective assessment of historic radon concentrations in Norwegian dwellings by measuring glass implanted Po-210--an international field intercomparison.

The first Norwegian study of historic radon concentrations in 17 dwellings in the high radon areas in Norway has been conducted as part of an international field intercomparison during 1998. The retrospective radon concentration is estimated via measurements of Po-210, the long-lived decay product of Rn-222 implanted in glass surfaces of objects like pictures, mirrors, cabinet-glass, etc. the method called 'surface trap'. Three different surface trap techniques to assess the implanted Po-210 activity and two different procedures to estimate retro radon from Po-210 data were used. The Po-210 and the retrospectively estimated radon results agree reasonably well over a wide range of concentrations. Historic radon concentrations were also estimated from analysis of a smaller number of 'volume trap' samples (pieces of spongy materials), and the results compared to those from 'surface traps'. The retro radon results correlate with contemporary radon results with a correlation coefficient of 0.877. To evaluate uncertainty in Po-210 measurements due to varying position on the glass a study of spatial homogeneity of three sample glasses was conducted and variations between 12% and 18% were found.

Integrated natural radiation exposure studies in stable Yugoslav rural communities.

The results of field investigations of natural radiation exposures of the general population in two stable rural communities in Yugoslavia are presented. The principal emphasis was on exposures to contemporary indoor radon, but measurements of external penetrating radiation absorbed dose rates in air were carried out in the majority of cases. In addition, in a limited number of dwellings, measurements of thoron gas concentrations were made. By means of making a series of sequential 3-month radon measurements, both seasonal variations and annual average radon levels in the dwellings were determined. Using passive alpha track detectors, individual radon and thoron indoor concentrations as high as 9591 Bq m(-3) and 709 Bq m(-3), respectively, were detected while absorbed dose rates in air in the dwellings as high as 430 nGy h(-1) were recorded. On the basis of these different types of measurements, assessments could be made of the integrated natural radiation exposures being received by the populations. In addition to contemporary radon measurements, retrospective radon exposure assessments in most of the dwellings were made on the basis of measurements of 210Po concentrations in both surface (glass) traps and in volume (porous materials) traps. A description is given of the sampling strategies and protocols used in this field work. It is shown that at least one stable rural community receiving high natural radiation exposures, has been clearly identified and plans for future health investigations of the population there are outlined.

Field experience with volume traps for assessing retrospective radon exposures.

Approximately 200 volume traps were retrieved from dwellings in various radon prone areas in Europe. They were analysed for the purpose of retrospective radon assessment. Emphasis is put on specific problems encountered when using field samples as opposed to laboratory exposed samples. It was seen that in very dusty circumstances, direct penetration of radon decay products from the outside to the centre of the volume traps calls for extra caution. Rinsing the samples is proposed as a solution and was tested in field and laboratory conditions, showing good results. An attempt was made to give an assessment of the achievable accuracy of the method. Where possible, the volume trap retrospective results were compared with contemporary measurements or to retrospective results from surface traps. The overall impression is that although volume traps are sometimes hard to find in the field, the high reliability of the results makes it well worth the effort.

Retrospective radon assessment by means of 210Po activity measurements.

A method for retrospectively assessing the average radon concentration in a dwelling, for a period as long as 40 years or more, is described. It is based on the free penetration of radon gas into bulky spongy materials called volume traps, and subsequent trapping of radon decay products inside them. This leads to a build-up of 210Pb, a radon decay product with a half life of 22.3 years, which reaches an equilibrium with the alpha emitter 210Po, indicative of the average radon concentration over the exposure period. The stuffing of mattresses, chairs, cushions, etc. can be considered a good volume trap. A chemical separation procedure is described, transforming the volume trap into a 210Po alpha source, whose activity is determined through alpha spectroscopy. The technique has been applied in over 300 samples, retrieved from dwellings in Serbia, Germany, Norway and Sweden. The technique has proven to be very robust and reproducible. In cases where radon data were available during the exposure period of the volume trap, a remarkable agreement was found. The best volume traps appeared to be polyester sponges found in many stuffings. The major drawback is the destructive nature of the method, its major advantage is the direct relationship between the radon gas and the 210Po signal. The technique can be useful in epidemiological studies of the lung cancer risk from indoor radon, for assessing the long term radon exposure.

The usability of wood as a volume trap for the purpose of retrospective radon exposure assessment.

The possibility of using wood samples as a retrospective radon monitor was investigated. Retrospective radon monitors are based on the analysis of the enhanced 210Po content of the bulk of the sample as a result of radon exposure. Several wood samples in different sizes and shapes were tested for their radon penetrability and the speed at which radon can diffuse throughout the material. Also, the volume ratio of air to solid material and the natural occurring 210Po background were determined. It was seen that only in fairly exceptional cases wood can be used as an acceptable volume trap. This is mostly due to the high and variably occurring natural 210Po background in wood samples with respect to the expected increase in radon-related 210Po due to common radon concentrations in dwellings.

Volume traps--a new retrospective radon monitor.

A new method to trace back average radon concentrations in dwellings over several decades in time has been developed. This retrospective radon monitor is based on the measurement of the alpha activity of 210Po deposited in volume traps, e.g., spongy materials used for mattresses and cushions. Polyester samples with different densities have been exposed to radon-laden air. The exposures correspond to characteristic radon concentrations between 390 Bq m-3 and 3.9 kBq m-3 over a 20 y period. The precision in converting the 210Po-signal to the radon exposure has been improved by more than one order of magnitude compared to other common techniques. It is shown that this very sensitive method may be applied to almost all types of volume traps used in households.

Modeling radon progeny absorbed in glass.

The depth distribution of 214Pb and 210Pb in glass was calculated from 218Po and 214Po deposited on the surface. The activity is found in a very narrow zone near the surface (< 100 nm). A fraction of the absorbed 214Po is capable of reaching the surface by decay into 210Pb. This fraction amounts to 29.8%.

Three-dimensional treatment of steady-state 222Rn diffusion in building materials: introducing a practical modified one-dimensional approach.

A three dimensional solution of the steady state diffusion equation, with boundary conditions applicable to closed can 222Rn exhalation measurements is described. A modified one-dimensional formalism is introduced which allows the interpretation of the results from exhalation measurements in terms of one-dimensional 222Rn exhalation from walls.

A closer look at the behaviour of radioactive decay products in air.

Apart from the "classical" processes like deposition, attachment and ventilation, we have also incorporated the clustering of condensable products around ions and the neutralisation of ions into the description of the behaviour of radioactive decay products in air. The interplay between these various processes and their effect on the active size distribution is studied by numerical model calculations.

The equilibrium of attached and unattached radon daughters in the domestic environment.

The Jacobi Room Model is applied to fit radon daughter concentrations measured in a room. The aerosol size distribution and ventilation rate are measured simultaneously. The mean deposition rate fitted to these experiments is 16 h-1. Once all parameters are fixed, the unattached fraction and the effective dose equivalent are calculated, and are put in perspective to the Working Level concept.