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Biomedical subjects

R G Dale

Publications and source records attributed to R G Dale.

72 records · Page 4Linked to original sources
PubMed1989

Antibody distribution and dosimetry in patients receiving radiolabelled antibody therapy for colorectal cancer.

The distribution of iodine-131 (131I) labelled antibody to carcinoembryonic antigen (CEA) has been studied in 16 patients with colorectal cancer. Levels of tumour and normal tissue radioactivity were measured by serial gamma-camera imaging and counting of blood and urine. Maximum concentrations were found in tumour 8 h after administration and varied up to 9-fold in different patients. Higher levels were found on average in tumour than in any other tissue. Liver, lung and blood were the other tissues in which antibody was concentrated relative to the rest of the body. Antibody cleared from all these tissues over 1 week. Second antibody directed against the antitumour (first) antibody was given 24 h after first antibody in order to accelerate clearance from the blood. This increased the tumour to blood ratio but had little effect on other tissues. Cumulative radiation dose to tumour and normal tissue was estimated. In patients with the most efficient localisation the tumour to body ratio was 20:1 and tumour to blood ratio 5:1. This may be sufficient for effective therapy of cancer in patients selected for efficient antibody localisation. The data may be used to estimate the effect of different therapeutic strategies. For instance, in the time after second antibody administration the average tumour to blood ratio of radiation dose was 11:1, suggesting that two phase systems in which the therapeutic modality is given after a good tumour to normal tissue ratio is obtained may be effective for the majority of patients.

Antibodies, Neoplasm↗
PubMed1989

Radiobiological assessment of permanent implants using tumour repopulation factors in the linear-quadratic model.

By combining existing linear-quadratic equations relating to decaying-source therapy with an assumed tumour repopulation factor, it has been possible to devise a method for the radiobiological assessment of permanent implants. For calculation purposes there is a time after which an implant can no longer be considered effective in sterilizing tumour cells. This "effective" treatment time for a permanent implant can be approximately defined in terms of the radionuclide decay constant, the potential doubling time, the initial dose-rate and the value of alpha in the tumour alpha/beta ratio. The analytical technique has been applied to a specific intercomparison of commonly encountered implants using 125I and 198Au, and suggests that, even in the most favourable cases, the former radionuclide offers few radiobiological advantages. Although not specifically discussed here, the method can also be applied to the assessment of various forms of biologically targeted radiotherapy.

Brachytherapy↗
PubMed1988

Repeated antitumour antibody therapy in man with suppression of the host response by cyclosporin A.

Antibody targeted therapy of cancer results in anti-antibody production which prevents repeated treatment. Cyclosporin A (CsA) has been used to suppress this response in patients treated with a radiolabelled antibody to carcinoembryonic antigen (CEA). Patients with CEA producing tumours received a minimum of two courses consisting of an injection of radiolabelled antibody and CsA, 24 mg kg-1 day-1, for 6 days; each course was given at 2 week intervals. Two weeks after the completion of the second course the mean human antimouse antibody (HAMA) levels were 3.5 micrograms ml-1 (s.d. 2.7) in 3 patients receiving CsA and 1,998 micrograms ml-1 (s.d. 387) in 3 patients not receiving the drug. Clearance of antitumour antibody was accelerated and tumour localisation absent when HAMA levels exceeded 30 micrograms ml-1. With lower levels of HAMA in the CsA-treated patients, further antitumour antibody accumulated in the tumour after each dose. Further therapy with antitumour antibody and CsA lead to the development of HAMA, but this was less than 25% of the amount in patients not given CsA. In this preliminary study up to 4 times as many doses of antitumour antibody could be usefully given when CsA was used. This increases the potential for effective antibody targeted therapy of cancer.

Adult↗
PubMed1988

Possible dose rate dependence of recovery kinetics as deduced from a preliminary analysis of the effects of fractionated irradiations at varying dose rates.

Data relating to jejunal crypt survival following fractionated total body irradiation of C3H mice have been subjected to a preliminary analysis using the linear-quadratic formalism. Because the regimes considered involved fairly closely-spaced fractions, delivered at dose rates in the range 1.2-72 Gy h-1, it was necessary to further develop previously established forms of the model in order to carry out the evaluation. The magnitude of the recovery half-life has been deduced for each of the regimes and found to be in the approximate range 0.1-0.6 h. For any given fraction number, the half-life appears to be markedly dependent on dose rate, increasing with dose rate up to approximately 25 Gy h-1, falling off thereafter. Tentative reasons for this behaviour are given, together with an assessment of the possible shortcomings of the analytical method.

Animals↗
PubMed1987

Use of second antibody in radioimmunotherapy.

In this study, a second antibody was directed against the first antitumor antibody to accelerate clearance of the 131I-labeled first antibody and improve tumor to normal tissue ratios of radioactivity. The value of this method in improving the therapeutic index of radioimmunotherapy with 131I-antibody to CEA has been investigated in nude mice bearing xenografts of human colon carcinoma and in 5 patients with colorectal cancer. The xenografts did not become saturated with anti-CEA as the administered dose was increased to therapeutic levels. At these high dose levels, the second antibody increased tumor to blood ratios to a maximum of 155:1, 48 times the level in controls that did not receive the second antibody. In 5 patients given 50 mCi of anti-CEA, there was no significant toxicity with the second antibody; clearance of radioactivity was accelerated; and tumor imaging was enhanced. The second antibody appears to have the potential to improve the therapeutic index of radioimmunotherapy.

Animals↗
PubMed1986

The application of the linear-quadratic model to fractionated radiotherapy when there is incomplete normal tissue recovery between fractions, and possible implications for treatments involving multiple fractions per day.

By extending a previously developed mathematical model based on the linear-quadratic dose-effect relationship, it is possible to examine the consequences of performing fractionated treatments for which there is insufficient time between fractions to allow complete damage repair. Equations are derived which give the relative effectiveness of such treatments in terms of tissue-repair constants (mu values) and alpha/beta ratios, and these are then applied to some examples of treatments involving multiple fractions per day. The interplay of the various mechanisms involved (including repopulation effects) and their possible influence on treatments involving closely spaced fractions are examined. If current indications of the differences in recovery rates between early- and late-reacting normal tissues are representative, then it is shown that such differences may limit the clinical potential of accelerated fractionation regimes, where several fractions per day are given in a relatively short overall time.

Cell Survival↗
PubMed1986

A graphical method to simplify the application of the linear-quadratic dose-effect equation to fractionated radiotherapy.

The linear-quadratic (LQ) dose-effect equation has been shown to be capable of providing a number of new insights into clinical radiotherapy. However, even in the most straightforward application of the formalism, i.e. to fractionated radiotherapy, the level of mathematics required to solve the associated equations could be a significant barrier to the wider application of the LQ method. In this paper it is shown that a wide range of problems arising in fractionated radiotherapy are capable of being analysed with the aid of one basic graph. It is further demonstrated that the extrapolated response dose, which forms the conceptual fulcrum of the LQ method is an additive quantity, and that the analysis of treatments involving several component parts can be simplified by using this property. The main features of these simplifications are demonstrated using some representative worked examples.

Brachytherapy↗
PubMed1985

The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy.

The linear-quadratic (LQ) dose-effect formalism is currently providing new perspectives into the ways in which alterations in the dose per fraction in conventional radiotherapy may be used to bring about improved results with respect to early or late normal tissue reactions. In this paper, using a model initially developed by Roesch, the LQ equations are explored further in terms of dose-rate rather than dose. By the incorporation of one other parameter, mu, which relates to the rate of repair of sub-lethal radiation damage, a more general formalism is obtained. In particular, equations are derived which can be used to examine the relative effectiveness of different treatment regimes, including those involving decaying sources. Such equations are of wider applicability than other LQ derivations which relate only to dose-response relationships. The extended equations, which are fully consistent with the existing LQ method, are also shown to lead directly to other independently established, relationships for protracted irradiation. The nature of the link between high and low dose-rate treatments is discussed, and some worked examples provide indications of how the new equations may be used to assess further the potential clinical benefits of low dose-rate treatments and permanent implants.

Carcinoma↗
PubMed1984

A Fortran program for fast and compact processing of clinical radiotherapy data.

A set of Fortran IV programs have been developed to enable a patient registry to operate on a minicomputer of a type frequently used for treatment planning within radiotherapy departments. The system is both comprehensive and flexible, allowing the efficient storage of clinical data in the form of coded units. The coding format used enables inexperienced operators to enter, or extract data from the system with the minimum of keyboard operations.

Computers↗
PubMed1982

A Monte Carlo derivation of parameters for use in the tissue dosimetry of medium and low energy nuclides.

A technique for deriving the tissue-absorbed dose resulting from the use of a selection of nuclides commonly employed in brachytherapy is given. The various parameters required have been obtained from a Monte Carlo computer program which derives tissue attenuation data from the equations of White and Fitzgerald (1977a). Some inconsistencies in the data used to obtain the equations are noted and corrected. Useful results are presented and, in particular, possible dosimetric errors associated with the clinical use of 125I seeds are highlighted.

Brachytherapy↗
PubMed1978

Implementation of the Philips treatment planning system for use in radiation teletherapy.

The Philips TPS is a dedicated computer system primarily for the calculation and display or radiotherapy dose distributions resulting from multiple field and rotational beam teletherapy techniques. Although a comprehensive range of planning facilities is offered by the system, including calculations in a number of parallel slices taken through the patient, the amount of basic data required to program the system is modest. This paper describes the beam checks which are necessary in order to obtain the input data, and then examines how well the computed radiation beams compare with independently measured isodose distributions. Other features of the system are discussed and an assessment of its operational reliability is given. The recently developed interstitial program is not examined here.

Computers↗
PubMed1976

Calculation by computer of dose distributions for superficial gold-198 implants and the derivation of optimized distribution rules.

A computer program has been written which provides two-dimensional visualization of the radiation dose distributions in the treatment surfaces aroung single-plane gold seed implants. The program was modified in order to investigate the uniformity of dose resulting from various patterns of seed arrangements, and, for a number of sizes of circular implants, practical loading schemes to produce minimum dose variations have been tabulated. Comparisons are made between dose distributions obtained from application of the derived data and those arising from application of the Paterson-Parker rules.

Computers↗
PubMedDate not supplied

Some theoretical derivations relating to the tissue dosimetry of brachytherapy nuclides, with particular reference to iodine-125.

Using a Monte Carlo computer technique, tables of parameters have been derived which are of use in the dosimetry of brachytherapy nuclides in a variety of tissues and organs. From the results, it has been possible to derive relationships linking the composition of a tissue with the dose received at any location around an implanted source. Other factors, such as the relative importance of scattered radiation, spectral degradation, and integral dose, are also discussed. In particular, attention is drawn to possible dosimetric problems arising from the clinical use of 125I.

Brachytherapy↗