1987 Douglas Lea memorial lecture. Particle dosimetry in bone and the toxicity of bone-seeking radionuclides.

Consideration is given to the tissues at risk in bone and a Monte Carlo method is described which determines the absorbed dose to endosteal tissues and marrow in trabecular bone. The method synthesizes random tracks through the trabecular structures that deposit energy along a path through any given trabecular cavity. The path lengths through the trabeculae and marrow cavities are measured with a bone-scanning microscope and other bone data, such as trabecular surface areas, can also be derived. Results are given for human bones and for bones of the beagle, miniature pig and rhesus monkey. They show that, for the same radionuclide concentration, the doses to endosteal tissues and bone marrow are several times greater in animal than in human bone, and that higher doses in human bone from the Ca and Sr radionuclides are obtained if the initial deposition on bone surfaces is allowed for. Other studies show that the occurrence of osteosarcoma in the human long bones correlates well with trabecular surface area and also that, unlike the case of beta-particles from 90Sr+90Y, leukaemia is not a significant consequence of the alpha-particle doses from 226Ra in human bone or from 226Ra, 239Pu and other alpha emitters in beagle bone.

Calculated beta-ray dose factors for trabecular bone.

Mean dose factors have been calculated for those tissues in bone that are relevant to the induction of late irradiation effects; namely, red bone marrow and endosteal tissues lining trabecular bone surfaces. The calculations are based on a Monte Carlo computer method for beta-emitting radionuclides which are distributed uniformly throughout the volume of mineralized bone. Results are given for the radionuclides 14C, 45Ca, 22Na, 18F, 32P, 90Y and 90Sr+90Y (all considered for this purpose as volume-seekers) for seven bones from the adult human skeleton and calculations are also presented of average skeletal dose factors. Where possible, results are compared with those derived from other methods based on simple geometrical models.

'Radial' scanning of trabecular bone: consideration of the probability distributions of path lengths through cavities and trabeculae.

Previous methods of dosimetry for radionuclides deposited in trabecular bone have been based on probability distributions of random path lengths through the trabeculae and marrow cavities. These distributions have been measured by a technique in which thin bone sections are effectively scanned along sets of parallel grid lines. A new technique is described in this paper, in which all scan lines pass through a selected point in the section scanned, so that they effectively radiate from the point (or focus) in the manner in which particles emerge isotropically from a radioactive atom. By scanning from a number of foci a 'radial-random' distribution can be obtained for a whole bone, and this distribution compared with that obtained from 'parallel' scanning. Differences between the two types of distribution have been observed, especially where the bone exhibits structural anisotropy, the effect on the lengths being up to 13% longer for the radial scanning mode. The effect on the calculated dose factors is not great; based on radial scanning, the factors for a lumbar vertebra are from 5 to 12% less than those for parallel scanning, depending on particle energy. The differences are very small for bones with more uniform trabecular structures, so that for the skeleton as a whole the differences will be smaller than those quoted.

Attenuation factors for certain tissues when the body is irradiated omnidirectionally.

Experimental values of mean attenuation factors are reported for certain tissues in an anthropomorphic phantom irradiated omnidirectionally with gamma rays from sodium-24, radium-226, iodine-131 and xenon-133. The data are used to relate the mean absorbed dose to the whole body, bone marrow, gonads and skin to (a) the absorbed dose in air and (b) the exposure in air. Correlations are made for the degradation of the radiation by scatter and the photoelectron enhancement effect. It is proposed that for natural background gamma rays a mean attenuation factor of 0.7 may be used for bone marrow. The corresponding rad/R factor is 0.67. It is also estimated that the effective mean depth of bone marrow for omnidirectional irradiation is 5.0--5.5 cm.

Measurements of trabecular bone structure in man.

A quantitative analysis of trabecular bone structure is presented, based on omnidirectional distributions of paths across (a) trabeculation and (b) marrow cavities. The omnidirectional distributions, which take into account structural anisotropy, are generated from measured distributions of paths. Representative examples are given, together with values of two commonly quoted structural parameters, the ratio of endosteal surface to bone volume and percentage bone volume. Data on the biological and age variations in the third lumbar vertebra are also presented and an index of trabecular anisotropy suggested. Finally, the results are compared with those of other workers and estimates of useful skeletal parameters given.

Calculated dose factors for the radiosensitive tissues in bone irradiated by surface-deposited radionuclides.

The method of calculating dose factors for the haemopoitic marrow and endosteal tissues in human trabecular bone, used by Whitwell and Spiers for volume-seeking radionuclides, has been developed for the case of radionuclides which are deposited as very thin layers on bone surfaces. The Monte Carlo method is again used, but modifications to the computer program are made to allow for a surface rather than a volume source of particle emission. The principal change is the introduction of a surface-orientation factor which is shown to have a value of approximately 2, varying slightly with bone structure. Result are given for beta-emitting radionuclides ranging from 171Tm (E (E beta=0.025 MeV) to 90Y(E beta = 0.93MeV), and also for the alpha-emitter 239Pu. It is shown that where the particle ranges are short compared with the dimensions of the bone structures the dose factors for the surface seekers are much greater than those for the volume seekers. For long range particles the dose factors for surface and volume-seeking radionuclides converge. Comparisons are given relating the dose factors calculated in this paper on the basis of measured bone structures to those of other workers based on single plane geometry.

Photoelectron enhancement of the absorbed dose from X rays to human bone marrow: experimental and theoretical studies.

A technique is described by which lithium fluoride powder is introduced into the marrow cavities in specimens of human trabecular bone to determine the excess photoelectron dose to marrow, when bone is irradiated by X rays of energies between 20 keV and 140 keV. Three specimens of trabecular bone, containing respectively 10, 15 and 25% bone by volume, were investigated and the results compared with those derived on the basis of earlier calculations for mono-energetic electrons by Whitwell. Reasonable agreement was found between the experimental and theoretical results, although there was some indication that scatter influenced the practical measurements at the higher photon energies. Theoretical calculations are then used to derive photoelectron dose enhancements for complete bones from the measured results on the bone specimens, and mean enhancements of the marrow dose for the whole human skeleton are calculated for subjects aged 44, 9 and 1.7 years.

Mean skeletal dose factors for beta-particle emitters in human bone. Part I: volume-seeking radionuclides.

Based on calculations by Whitwell and Spiers, mean skeletal dose factors for beta-particle emitters have been derived for application to dosimetry in nuclear medicine, radiobiology and radiation protection. The dose factors apply to bone-seeking radionuclides that are depostited more or less uniformly throughout the human mineralized skeleton and are defined as: (1) vDM/DB, the mean dose to the haemopoietic marrow in trabecular bone as a fraction of the "dose to bone", DB; (2) vDs/DB, the mean dose to endosteal (osteogenic) tissue lying in a zone 0--10 micron from trabecular surfaces, also as a fraction of the dose DB. Dose factors are given for three ages, 1.7, 9 and 44 years and for eight radionuclides, ranging in mean beta-particle energy from 0.05 MeV (14C) to 0.93 MeV (90Y). Dose factors, calculated for a single lumbar vertebra of an infant aged 3.5 weeks, enable approximate values of mean skeletal dose factors to be estimated for ages less than 1.7 years. Limited data are also reported on dose factors for the femoral cortex from subjects aged 9 and 50 years.

Measurements of endosteal surface areas in human long bones: relationship to sites of occurrence of osteosarcoma.

Using techniques of bone scanning and ashing, the areas of the endosteal surfaces in cortical and trabecular bone have been determined for the proximal, mid and distal thirds of each of the six long bones of an adult human subject. The relative frequency of occurrence of bone sarcomas, scored as to site, has been analysed in relation to these measured areas. Data on tumour occurrence have been drawn from three sources: radium-case data from Rowland and Keane (33 cases), naturally-occurring cases from series by Sissons (139 cases) and by Dahlin (473 cases). A strong correlation is demonstrated between tumour frequency and trabecular area, but correlation with cortical area is poor. By comparing the tumour frequency in the mid thirds of the bones with the total recorded it has been possible to show that the probability of tumour occurrence per unit area of cortical bone, relative to that of trabecular bone, is 0.16 +/- 0.06. Analysis of the available dose data for the radium cases shows that in this instance dose has not contributed to the observed correlations. The results lend support to the thesis that tumour occurrence depends on surface area, i.e. on the number of cells at risk.

The absorbed dose to bone marrow in the treatment of polycythaemia by 32P.

This paper reports the determination of absorbed dose to bone marrow in the treatment of polycythaemia by 32P, based on the measurement of activities in bone and marrow biopsies taken at various times from 1 to 27 days after injection of the radionuclide. Activities were measured in the cortex, trabeculation and marrow of biopsies taken from the iliac crest, and slso in sternal marrow. The biological half-life of 32P in marrow from the iliac crest was found to be nine days; that derived for sternal marrow was lower, but the difference was not statistically significant; the value for trabecular bone was 27 days. The biological half life for 32P in the body, as measured by whole-body counting, was 39 days. Calculations of the dose-rate to trabecular marrow have been made by a method based on that of Whitwell and Spiers (1971), but modified to allow for the presence of32P in the marrow as well as in trabecular bone. The dose-rates follow a single exponetial decay with a half-life of 6.7 days. The intergrated dose including that during the first day is 24 rad per mCi injected.

Mean skeletal dose factors for beta-particle emitters in human bone. Part II: surface-seeking radionuclides.

Mean skeletal dose factors for surface-seeking beta-emitting radionuclides have been derived on the basis of the beta-particle dose factors calculated for human bones by Spiers et al. (1978b), or from empirical formulae representing these calculations given by Beddoe and Spiers (1979). The dose factors are derived for the same tissues as in Part I (Spiers et al., 1978a), namely, (1), sDM/Dskel, the mean dose to haemopoietic marrow in trabecular bone, and (2), sDs/Dskel, the mean dose to endosteal tissues lying in a zone 0-10 microns from trabecular surfaces. The dose factors are given as fractions of Dskel, the "dose to bone", calculated from the energy released by the retained radionuclide divided by the total mass of mineral bone. As in Part I, the dose factors are given for three ages, 1.7, 9 and 44 years and extrapolation to lower ages is made on the basis of calculations for a lumbar vertebra of an infant aged 3.5 weeks. The factors are given for six radionuclides covering a range of mean beta-particle energies from 0.0255 MeV (171Tm) to 0.93 MeV (90Y). The dosimetry is also considered for some radionuclides that first deposit on bone surfaces before being translocated to the bone volume. In the case of 45Ca, for example, it is shown that the dose calculation that includes both the surface and the volume depositions gives integrated doses to ten days and 100 days that are respectively 4.5 and 1.9 times the corresponding values calculated conventionally on a volume deposition only. Endosteal dose factors are similarly considered, and other radionuclides included as surface-plus-volume depositions are 47Ca, 89Sr and 90Sr + 90Y.

Sites of incidence of osteosarcoma in the long bones of man and the beagle.

Information has been assembled on the frequency of occurrence of osteosarcomas in the long bones of groups of beagles irradiated by alpha particles from bone-seeking radionuclides. These data are compared with measured trabecular surface areas in the long bones of a beagle, determined at the Bone Dosimetry Research Laboratory, Cookridge Hospital, Leeds. It is shown that, as in the human case, the percentage tumour occurrence in a long bone (or in separate thirds of a long bone) was linearly related to the corresponding trabecular surface area with a high value of the correlation coefficient. For single injections of 226Ra the low percentage tumour occurrence in the mid-thirds of the beagle bones was close to that found in man. For the surface-seeking radionuclides (239Pu, 228Th) and for 228Ra much higher percentages of tumours were found in the mid-thirds of the dog bones than for 226Ra injection. When, however, 226Ra was given in eight fractions with 14 days between each injection, a very high tumour incidence was found in the mid-thirds of the beagle long bones. These results are discussed in the light of dosimetric and other relevant factors.

Leukaemia incidence in the U.S. dial workers.

Late biological effects of radium deposited in the human skeleton have manifested themselves unequivocally as osteogenic sarcomas or carcinomas of the mastoid air cells or paranasal sinuses. On the basis of current estimated risk factors, it might be expected that an excess of certain other malignancies could occur in a population of the size of the group exposed to radium (some 3500 cases located, which more than 2000 have measured 226Ra and 228Ra burdens), compared with the incidence in the population at large. An increased incidence of breast cancer has already been reported in female dial workers and it was related to the initial radium intake. On the other hand, very little information is available on the induction of leukaemia by alpha-radiation in human bone marrow. This paper therefore reports an investigation of the incidence of leukaemia among the radium workers. This covers a very wide range of radium burdens and has been done in the light of reasonable estimates of the mean alpha-particle dose received by the skeletal haemopoietic marrow. The number of leukaemia cases is identified and compared with (a) the expected number in a comparable population of the same size and age distribution and (b) predictions based on the risk factor proposed for protection purposes by the ICRP and on the estimated bone marrow doses.