Volume 89, Issue 4-5 - Nuclear Data for Medical Applications

A brief introduction to nuclear data in medicine is given. The choice of a radioisotope for medical application demands an accurate knowledge of radioactive decay data. Short-lived single photon and β + -emitters are preferred for diagnostic investigations, and longer-lived corpuscular radiation emitting radioisotopes for endoradiotherapy. The nuclear reaction cross section data, on the other hand, are needed for optimising the production routes. Besides radioactive isotopes, the use of ionising radiation in therapy is discussed. External radiation therapy has achieved an important place in medicine. The role of nuclear data is briefly discussed; they are needed for radiation dose calculations. The hitherto rather neglected activation products in proton therapy are considered. The methodology of development of a nuclear data file for medical applications is outlined

This paper summarizes the various nuclear data types and libraries available free of charge from the IAEA Nuclear Data Section, many of which are relevant to medical applications. The databases are collected, maintained and made available within the framework of an international nuclear data centers network. Particular emphasis is given to online services via the Internet. The URL address of the IAEA Nuclear Data Services is http://www-nds.iaea.or.at .

Nuclear medicine methods permit the visualisation of a variety of metabolic and physiological processes all over the body. Although planar scintigraphy has been found useful for many questions, detailed spatial information about the diseased organ can only be obtained with tomographic methods. Dependent on the radionuclide involved, two different tomographic procedures are available: single photon emission computed tomography (SPECT) and positron emission tomography (PET). The first part of this paper describes shortly the historical development of these methods as well as their technical and methodological basics. To elucidate the large variety of possible applications, an overview of SPECT and PET procedures utilised in research as well as in clinical practice are presented. Furthermore, both methods are compared and their individual advantages are pointed out.

Nuclear medicine methods permit the in vivo measurement of physiological and metabolic functions. For this purpose metabolically active molecules are labelled with radionuclides. After the injection, these radiopharmaceuticals can be detected from outside the body with appropriate detectors such as conventional gamma cameras, single photon emission computerized tomographs (SPECT), or positron emission tomographs (PET). As with any application of ionizing radiation the benefits of nuclear medicine (the diagnosis and treatment of disease) must be balanced against the risks of the procedures. Risks in nuclear medicine are evaluated through dosimetry, the calculation of the radiation dose estimates, in which the energy deposited by the radiation in human tissues is quantitated. The first step of dosimetry is the determination of the biodistribution, i.e. the spatial and temporal distribution of the radiopharmaceutical within the body. When a new radiopharmaceutical is introduced such data are first derived from ex vivo experiments in animals. Further evaluations of the biokinetics and dosimetry are carried out via quantitative measurements in humans using the nuclear medicine imaging equipment, applying whole-body planar and tomographic methods. Based on the knowledge of the biodistribution and using the framework introduced by the MIRD committee as well as by the ICRP, the radiation dose to single organs and to the total body can be calculated. The purpose of this paper is to review methods for measuring radiopharmaceutical biodistributions in humans and for calculating the appropriate radiation dose quantities.

The types of nuclear data and their quality required in the production and application of diagnostic radionuclides are outlined. The radioactive decay data determine the suitability of a radioisotope for in vivo tracer studies, both from the imaging and internal radiation dose considerations. The nuclear reaction cross section data allow optimisation of production routes. Both reactors and cyclotrons are used for production purposes. The nuclear data needed in the two cases and their present status are discussed. Special attention is paid to radionuclides suitable for emission tomography (PET and SPECT). The controversy about reactor vs cyclotron production of the widely used 99 Mo/ 99m Tc generator system is discussed. Some special considerations in cyclotron production of radionuclides are outlined. The need of accurate data near reaction thresholds, the constraint of available particles and their energies at a small cyclotron, the influence of increasing incident particle energy, and the formation of isomeric impurities are discussed in detail. The role of nuclear model calculations in predicting unknown data is considered.

The rationales for hadron therapy are based on the physical selectivity and biological effects of the respective beams. Fastneutron therapy began as long ago as 1938 and subsequently proton, alpha particle, heavy ion, pion and neutron capture therapy have beenused. To date it is estimated that in excess of 50000 peoplehave undergone some form of hadron therapy. In the future it isexpected that fast neutron therapy will be used for selected tumourtypes for which neutrons are known to show improved cure rates. Thefuture trends in charged particle therapy will be driven by increasingcommercialization. The future of neutron capture therapy will dependon current clinical trials with epithermal neutron beams and thedevelopment of new tumour-seeking drugs.

The safety, efficacy and reliability of photon beams is well established; however, new types of beams continue to be introduced and explored with the aim of achieving improved selectivity from better dose distribution or from radiobiological mechanisms. Fast neutrons were the first non-conventional radiation used in cancer therapy. Fast neutrons, a form of high-LET radiation, were introduced for the following radiobiological reasons: (1) a reduction of the OER with increasing LET, (2) a reduction in the difference in radiosensitivity related to the position of the cells in the mitotic cycle, (3) less repair and thus less clinical relevance of the different repair mechanisms. The best, clinically proven, indications for fast neutrons are salivary gland tumours, locally advanced prostatic adenocarcinomas and slowly growing, well differentiated sarcomas. Proton beams brought a significant improvement in the physical selectivity. Worldwide, the number of proton therapy centres in operation and in the planning stage increases continuously. The best clinical results so far have been reported for uveal melanoma, tumours of the base of skull, and some brain tumours in children. Heavy ions combine the advantage of better physical selectivity of protons with the radiobiological advantages of fast neutrons for some tumour types. Heavy ions were applied at Berkeley from 1975 to 1992, and at NIRS in Chiba since 1994. A pilot study started at GSI-Darmstadt in 1997. Boron neutron capture therapy (BNCT) aims at a physical selectivity at the cellular level; it is still in an experimental phase.

An attempt is made to formulate the requirements for the accuracy in the delivery of absorbed dose to a patient during radiation therapy. These requirements are mainly based on the relative steepness and separation of the dose-effect curves for local tumour control and normal tissue damage. The curves for normal tissue complications in general may be steeper than those for local tumour control. From these data, a standard requirement of 3.5% is proposed for the combined uncertainty of type A (random) and type B (systematic), given as one relative standard deviation in the absorbed dose delivery. However, it is recognized that, in many cases, larger uncertainties are acceptable palliative treatments). This value of 3.5% applies to the absorbed dose at the specification point for curative treatments. As far as the dose accuracy requirements at other points in the planning target volume are concerned, a value of 5% (one standard deviation) seems more appropriate. This required accuracy in the delivery of the absorbed dose cannot always be completely achieved in photon therapy even for simple treatment conditions. All the clinical data which were reviewed, including some results from the ldquo;Patterns of Care Study”, indicate a close correlation between the outcomes of therapy (control rates, complications) and dose level, inaccuracy or errors in dosimetry and patient-machine positioning. This has been reported for external beam therapy as well as for brachytherapy. Only the clinical results will allow us to select the optimal treatment conditions (e.g. selection and definition of the planning target volumes, dose levels and beam arrangement), but they could be interpreted correctly only to the extent that the treatment execution would be correct. This result strongly endorses the Quality Assurance Programmes, in which the clinicians and physicists should be fully involved. Lastly, the outcome of a treatment can only be interpreted meaningfully if the parameters of the irradiation, in particular, the distribution of dose in space and time can be accurately correlated with the type and extent of the disease. It is essential that clear, well defined and unambiguous concepts and parameters be used for reporting purposes to ensure a common language between collaborating centres. This is one of the major tasks that the ICRU undertook several years ago.

Neutrons from the reactions of protons or deuterons of energies between 35 and 70 MeV on beryllium are most suitable for therapy because of the high yield and good penetration. Lower energy sources are used for limited applications. Proton therapy is conducted mainly in two energy ranges, viz. 60–75 MeV (exclusively for the treatment of eye lesions) and ≥200 MeV for general applications. Characterisation of both neutron and proton therapy beams in terms of spectral fluence is important for accurate determination of dosimetry parameters, for interpreting biological effects, for intercomparison purposes and to perform accurate radiation transport calculations.

Fast neutrons and protons undergo fundamentally different interactions in tissue. The former interact with nuclei, while the latter, as in the case of photons, interact mainly with atomic electrons. Protons do, however, also undergo some nuclear reactions, the probability of which increases with proton energy. The determination of the reference absorbed dose in a patient for the two modalities is described. Two internationally accepted protocols have been formulated and have been published in ICRU reports. For both modalities the practical means for determining the reference absorbed dose in a patient involves the use of thimble ionization chambers calibrated in 60 Co beams.

The range and status of nuclear data on the interaction of medium-energy neutrons and protons with biomedical materials are discussed. Microscopic data (cross sections) include results of experimental measurements, indices and compilations of such data, and evaluated data. Experimental data, while usually available only in partial ranges of interest, are essential for validating and normalizing nuclear models used to produce comprehensive evaluated data libraries. Integral measurements of radiation transport such as depth-dose curves and of KERMA coefficients test the data and their application in transport calculations.

The nuclear data required for the production and endotherapeutic application of radionuclides are outlined. The three types of therapeutic radionuclides, viz. β - -emitters, α-emitters and Auger electron emitters, are considered and the role of some β + -emitters in therapy planning is discussed. The status of available data is reviewed.

A brief outline of nuclear reaction mechanisms including the optical model, the Distorted Wave Born Approximation, the Coupled Channels, classical and quantum-mechanical preequilibrium models and the Compound Nucleus is given. The relations among different nuclear reaction and structure models are indicated. The paper is addressed to the users of nuclear data and seeks to explain basic physical concepts and the role of nuclear reaction models in data evaluation.

A review of recent results on the model calculations and evaluations connected with the development of a reference charged particle cross section database for medical radioisotope production is presented. Nuclear reaction models and codes used in those investigations are briefly outlined, with examples of a few calculation results. The method of statistical optimization of experimental data, based on discrete optimization with rational functions (Pade approximation) is described, and the results of evaluations of excitation functions are presented.

This review article provides an overview, for medical physicists, of recent work that addresses the role of nuclear reactions in proton, fast neutron, and conventional photon radiation therapy. Nuclear reaction cross sections have been evaluated, in ENDF format, for use in Monte Carlo radiation transport simulations of radiotherapy, in order to optimize the absorbed dose to a tumor. The evaluations utilize both measured cross section data as well as nuclear model calculations of direct, preequilibrium, and Hauser-Feshbach compound processes. In the case of photonuclear reactions, giant dipole resonance and quasideuteron photoabsorption mechanisms are considered.

The Monte Carlo code MCNP (Monte Carlo N-Particle) has a significant history dating to the early years of the Manhattan Project. More recently, MCNP has been used successfully to solve many problems in the field of medical physics. In radiotherapy applications MCNP has been used successfully to calculate the bremsstrahlung spectra from medical linear accelerators, for modeling the dose distributions around high dose rate brachytherapy sources, and for evaluating the dosimetric properties of new radioactive sources used in intravascular irradiation for prevention of restenosis following angioplasty. MCNP has also been used for radioimmunotherapy and boron neutron capture therapy applications. It has been used to predict fast neutron activation of shielding and biological materials. One area that holds tremendous clinical promise is that of radiotherapy treatment planning. In diagnostic applications, MCNP has been used to model X-ray computed tomography and positron emission tomography scanners, to compute the dose delivered from CT procedures, and to determine detector characteristics of nuclear medicine devices. MCNP has been used to determine particle fluxes around radiotherapy treatment devices and to perform shielding calculations in radiotherapy treatment rooms. This manuscript is intended to provide to the reader a comprehensive summary of medical physics applications of the MCNP code.