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Book review |
This report is a comprehensive re-appraisal of absorbed dose specification as applied in nuclear medicine. It is common practice, at present, to use mean absorbed dose to assess radiological risk or to quantify the efficacy of a therapeutic procedure, with the underlying assumption that the radionuclide is distributed homogeneously within the target tissue. It is unusual for any assessment to be made of the effect of the varying dose rate as the dose is delivered. With regard to radiological risk, the question is whether mean absorbed dose provides an appropriate prediction of the risk. (In one example noted in the report, Auger electron emitters incorporated in the DNA chain were found to be more radiotoxic than expected from the mean absorbed dose.) The report examines the consequences of non-uniform distributions of radioactivity, variation in dose rate and its effect on biological response, the need for individual rather than standardized dose estimates (particularly in targeted radionuclide therapy), and advances in technology that facilitate more accurate measurement of the parameters that determine absorbed dose. The MIRD schema, along with its strengths and limitations, are reviewed.
After the Executive Summary and Introduction, the bulk of the report is contained in four chapters and two appendices. The first of these chapters is a review of the biological responses to ionizing radiation, dealing with DNA damage and repair, chromosomal aberrations, germ-cell damage, developmental defects, carcinogenesis and response to therapy. Unlike external beam therapy, irradiation from internal radionuclides is characterized by declining dose rates and marked discontinuities in dose distribution and hence there is a need to understand how biological responses are affected by dose distributions in space and time. Several aspects of radionuclide therapy are discussed. For instance, a feature of most therapeutic radionuclides is that the radiation dose is delivered at a low rate with an effective half time of days, which is long compared with the repair half-time for cultured mammalian cells (range minutes to hours). This renders the dose less effective than an acute dose of the same magnitude. It is also noted that fractionation and protraction of external beam therapy are thought to allow previously hypoxic cancerous tissue to re-oxygenate, hence reducing radioresistance. In order to achieve the benefits of re-oxygenation, targeted radionuclide therapy would require to be fractionated, which poses practical difficulties, although multiple administrations in animal models have been shown to mimic fractionation. Tumour size and the uniformity of uptake also influence therapeutic effectiveness. The report points out that there is a conflict in the requirements of an ideal radionuclide: one with short range emissions would be best for microscopic disease whereas one with long range emissions would be best if the radionuclide distribution is non-uniform. Hence the reason for the proposed use of "cocktails" of radionuclides.
The next chapter is a description of the MIRD schema, which is widely used within the nuclear medicine community. In considering its strengths and limitations, the report reiterates that the MIRD schema was originally devised to produce mean organ doses in diagnostic procedures for the assessment of risk. However, more recent adaptations have included the calculation of cellular "S" values and the use of a revised model of the adult head and brain to produce regional "S" values. The use of a constant "S" value is inappropriate in situations where the mass of the target may change whilst the radionuclide is still present (e.g. an irradiated tumour undergoing growth or shrinkage).
Dosimetric aspects of non-uniform distributions of radioactivity are covered in the next chapter. Included also is basic information on the different types of radionuclide decay processes, the corresponding radiations emitted, and the energy deposition and range of the same in tissue. There are several figures illustrating non-uniform uptake within assorted tissue elements. Some of the distribution data are tabulated, with one of the tables showing the subcellular distribution of several common radiopharmaceuticals. In the case of 99Tcm pertechnetate, for example, 93% of the cellular activity is contained in the cytoplasm and 7% in the cell nucleus, with half of the latter localized on the DNA. The dosimetric consequences are significant. In one of the examples given in the report, it was shown that 99Tcm albumin colloid concentrates in macrophages in the spleen and liver of mice. These cells occupy only 0.1–1% of the total volume of the organ and consequently receive absorbed doses that are 10–60 times those to surrounding cells. The increasing awareness and observation of non-uniform distribution of radionuclide has led to more sophisticated modelling and hence regional "S" factors including subcellular "S" factors for alpha particles and Auger electrons.
The chapter ends with a review of models used to describe the time course of radionuclide in the regions of interest and methods used to control, and alter, the same. Guidance is given on extrapolation of animal data to humans.
The final chapter includes an overview of the techniques used to quantify radionuclide uptake and to determine its localization volume. Published work on the use of SPECT and PET in these areas is reviewed as well as techniques used to compare estimated with actual measurements of absorbed dose. The question of individual patient dosimetry is addressed, the main requirements being: (1) knowledge of the anatomy (CT or MRI image set); (2) knowledge of the radionuclide distribution (SPECT or PET image set); (3) method of linking these two together with co-registration of the image sets; (4) method of calculating absorbed dose. In other words, the practical implications are not inconsiderable and would place a substantial strain on resources.
Appendix 1 explains the concept of biologically equal effective dose and its application in radionuclide therapy as against external beam therapy. In essence, it is a means of assessing the effectiveness of absorbed doses delivered in high dose rate fractions or, in the case of radionuclide therapy, delivered continuously with a declining rate, taking into account the ability of cells to repair. Appendix 2 contains basic decay schemes for a few radionuclides used in nuclear medicine. However the schemes lack detail, there being a paucity of data on the nature of the emissions, their intensity and energy.
In summary, the report succeeds in being a comprehensive review of the challenges facing the specification of absorbed dose in state-of-the-art nuclear medicine. With around 600 references it is unlikely that any relevant or significant work has been excluded. Whether it should found in the bookshelves of all nuclear medicine departments is debatable. However, units specializing in unsealed radionuclide therapy should find the report interesting and helpful.
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