Amos Norman

A localized current field hyperthermia system for use with 192‐iridium interstitial implants

The efficacy of localized current field (LCF) hyperthermia as an adjunct to 192Ir interstitial implantation of tumors is currently under investigation. In this article, we describe an experimental LCF system suitable for such investigations, and discuss some of the physical and biological parameters pertinent to its design and safe operation.

Radiation dose enhancement in tumors with iodine

The loading of tissue with iodine can result in the enhancement of the radiation dose absorbed from low-energy x-ray or gamma ray sources. We have explored the potential of this phenomenon for radiation therapy. We have demonstrated the effect of iodine concentration and radiation quality on this dose enhancement in lymphocytes, we have calculated the effect of such enhancement on depth dose distributions in the brain, we have estimated the iodine content in two human brain tumors during computerized tomography (CT) scans, we have studied the dispersion of the iodine contrast media after direct injection into rabbit tumors, and we have demonstrated that the combination of x-ray and contrast media injection is far more effective than either agent alone in causing the regression of mouse tumors. These results suggest that there may be a therapeutic advantage from loading tumors with iodine and treating them with low-energy photons.

Unscheduled incorporation of thymidine in ultraviolet-irradiated human lymphocytes.

The nature, degree, and kinetics of unscheduled thymidine incorporation previously shown to occur in 90 % of irradiated lymphocytes was stud-incorporation was sever ely depressed i n t h e presence of 10(-4) M acriflavine and by low temperature, but was unaffected by 10(-3) M hydroxyurea or caffeine. Over a dose range of 25 to 400 ergs/mm2, the uptake of thymidine was increased by a factor of only 1.6, although the survival of lymphocytes, measured 5 days after irradiation, decreased by almost two orders of magnitude. (The survival curve suggests that 90% of the lymphocytes have a D0 of 35 ergs/mm(2) and 10 % have a D0 of 250 ergs/mm(2).) After exposure to 25 ergs/mm(2), over 70 % of the cells survived for 5 days in culture; moreover, cells which had been stimulated by this dose to incorporate thymidine transformed and divided after exposure to phytohema-glutinin. The final uptake of thymidine was significantly greater when a total dose of 75 ergs/mm(2) was fractionated into three doses of 25 ergs/mm(2) given at six hourly intervals than when it was given as a single dose. The degree of thymidine incorporation and the fraction of leukemic cells labeled were not significantly different from those in normal lymphocytes.

Radiation Stimulated Incorporation of Thymidine into the DNA of Human Lymphocytes

TRITIATED thymidine is incorporated into both strands of DNA in HeLa cells which have been exposed to ultraviolet and ionizing radiation1,2. This stimulated incorporation can occur in concentrations of hydroxyurea3 which inhibit normal DNA synthesis.

Dose distributions using kilovoltage x-rays and dose enhancement from iodine contrast agents

In x-ray phototherapy of brain tumours, the tumour is loaded with iodine and exposed to kilovoltage x-rays. Due to the high photoelectric cross sections of iodine, substantial photoelectric interactions occur. The flux of photoelectrons, characteristic x-rays and Auger electrons produce a localized dose enhancement. A modified computed tomography scanner, CTRx, can be used both for tumour localization and delivery of the dose enhancement therapy. Monte Carlo methods were employed to simulate the treatment of iodinated brain tumours with a CTRx. The calculated results reveal the effect of tumour iodine concentration on dose distribution, the degree of skull bone sparing with the application of multiple arcs, and the homogeneity of tumour dose distribution versus iodine concentration. A comparison with 10 MV stereotactic radiosurgery treatment shows the potential of CTRx treatment relative to conventional treatment modalities.

Chromosome-exchange Aberrations in Human Lymphocytes

SummaryThe probability of finding a given chromosome in a dicentric is directly proportional to the length of that chromosome at interphase, but not to the length of the early replicating portion of the interphase chromosome or to its length at metaphase. The number of dicentric chromosomes and centric rings per cell is limited primarily by the number of centromeres. These results are consistent with the assumption that every chromosome break is a site for chromosome-exchange.

Cytogenetic Effects of Contrast Media and Triiodobenzoic Acid Derivatives in Human Lymphocytes

Micronuclei counts in blood samples from 9 patients before and after angiocardiography have confirmed previous results suggesting the diatrizoate contrast medium was largely responsible for the observed cytogenetic damage. To discover the agents in the medium causing the cytogenetic damage, we exposed human lymphocyte cultures to diatrizoate and to the monoamino- and diamino-derivatives of triiodobenzoic acid. The results show the amino-derivatives are capable of inhibiting mitosis and inducing micronuclei and chromosome aberrations at lower concentrations than diatrizoate.

Selection against chromosome aberrations in human lymphocytes.

THE frequency of chromosome aberrations in the lymphocytes of people who have been exposed to ionizing radiation decreases for many years, beginning some 2–3 weeks after irradiation, at a rate that depends on the type of aberration1,2. Differences in the rates at which the various types of aberration are eliminated are probably caused by differences in the selection against these aberrations at cell division. No data, however, have been reported on the probability that a given aberration in a human lymphocyte will survive cell division. In this communication we present such data obtained in vitro, together with some new data on the elimination of aberrations in vivo. The two sets of data suggest that the lymphocyte, when stimulated to divide in vivo, will undergo several successive divisions.

First radiotherapy of human metastatic brain tumors delivered by a computerized tomography scanner (CTRx)

PURPOSE This Phase I study was designed to evaluate the computed tomography (CT) scanner as a device for radiation therapy of human brain tumors (CTRx). This first use in humans of a modified CT for treatment was founded on extensive research experience with canine tumors. An additional objective was to increase the therapeutic radiation dose to tumors compared to normal tissue by concentration of infused contrast material in tumors, an effect available at diagnostic x-ray energies but not at megavoltage energies. METHODS AND MATERIALS A small metastatic brain tumor in each of eight patients received 3-5-weekly fractions of 5 Gy equivalent per fraction from a CT scanner modified to deliver radiation therapy. In each patient, one additional tumor, lying completely outside the volume treated by CTRx, served as a control. The tumor receiving CTRx was treated after infusion of iodinated x-ray contrast media (CM) for dose enhancement. Many of these patients also received conventional 40 Gy whole brain radiation, before, during, or after CTRx treatment. RESULTS None of the patients showed adverse reactions to the CM or necrosis of the normal brain from the CTRx boost radiation. Monte Carlo calculations of the radiation dose distributions in a model tumor showed that the CTRx irradiation of tumors carrying 10 mg or more of iodine per gram of tumor was as good or better than the dose distribution from conventional 10-MV X-rays. The treated tumor in two of the patients vanished after four treatments, whereas a control tumor in one patient remained constant and grew 4-fold in another patient. CONCLUSION The CTRx concept effectively combines a modified CT scanner as a diagnostic device, as a simulator dedicated to radiotherapy, and as a treatment machine. Thus, CTRx could be very useful for radiation oncologists in controlling CM-enhanced and other small brain tumors.

Effect of Radiation and Contrast Media on Chromosomes

Measurements of chromosome aberrations or micronuclei in lymphocytes obtained from 7 patients indicate that angiocardiography produced chromosome damage corresponding to an average absorbed dose of about 50 rads. This is an order of magnitude larger than was estimated from the exposure rate. Experiments on lymphocytes suspended in solutions of methylglucamine and sodium diatrizoate (Renografin) or sodium diatrizoate alone (Hypaque) indicate that the chromosome damage observed in the patients is due in large part to two effects: (a) an increased absorption of x rays as compared to blood and (b) a breakage of chromosomes even in the absence of x rays.