Leon S. August

Cesium-129 Myocardial Scintigraphy to Detect Myocardial Infarction

Cesium-129 is concentrated in the myocardium after intravenous administration permitting myocardial imaging. The dosage used was 2-2.5 mCi in dogs and 3-4 mCi in patients. Four or more views with 200,000 counts per view were obtained 30 to 90 minutes after administration. Control images were obtained in 30 dogs. In two dogs anatomic landmarks were obtained using technetium-99m markers. In 24 dogs, either the anterior descending or circumflex coronary artery was ligated. An area of absent uptake of 129Cs was seen involving the anterior wall and apex or the inferior-posterior wall, respectively. At postmortem this represented a myocardial infarction (MI) averaging 4×5 cm. Smaller MI (2×3 cm) at postmortem were seen as defects of the anterior wall. Evolution of an acute MI was followed in four dogs. The defect appeared at one hour and gradually increased on serial images. Fifty patients were studied. Each of 20 patients without evidence of MI had the normal horseshoe or doughnut appearance of the left ventricle surrounding the interventricular cavity. Each of 15 patients with acute MI and 10 of the 13 patients with an old MI had a defect on the myocardial image. The three patients without defects had infarction of the inferior wall. One of two patients with coronary insufficiency had a defect. These studies show that good quality myocardial images were obtained with 129Cs and strongly suggest its potential usefulness in quantification of an acute MI.

Radiobiological Properties of High—Energy Cyclotron-Produced Neutrons Used for Radiotherapy

Radiobiological properties of high-energy cyclotron-produced neutrons were investigated. The survival curve for mammalian cells exposed to 35 MeV neutrons has an appreciable shoulder, but exhibits a significant initial slope at low doses. split-dose experiments, using doses comparable to the daily fractions of neutron therapy, indicate no repair of sublethal damage. The nitroimidazoles, and particularly Flagyl, have been shown to selectively sensitize hypoxic cells to the effects of x-rays. Experiments demonstrated that Flagyl is equally effective in reducing the oxygen enhancement ratio for high-energy neutrons. Hypoxic sensitizers must by regarded as an adjunct to neutron therapy, rather than as a competitor.

Effects of myocardial hypoxia and ischemia on myocardial scintigraphy

The effect of regional myocardial ischemia and hypoxia on myocardial scintigraphy was studied in patients and dogs after intravenous administration of cesium-129. Seven men with angiographically proved ischemic heart disease underwent exercise testing and 129Cs was given immediately when ischemia was manifested in the electrocardiogram. Defects were not evident in the scintigrams of any patient. Failure to visualize a defect might be related to delayed uptake of 129Cs by the myocardium (maximal uptake in 45 minutes). The ischemic state was dissipated before the disparity in uptake between normal and ischemic myocardium could be visualized. Cesium-129 is useful for identifying acute myocardial infarcts but should not be used to visualize transient exercise-induced regional ischemia. Six dogs were given 129Cs after induction of regional myocardial hypoxia by perfusion of the anterior descending coronary artery with venous blood. In each, scintigraphy revealed a defect that resolved after reperfusion with arterial blood. Two other dogs were given 129Cs before perfusion with hypoxemic blood; neither dog manifested a defect. Since perfusion was maintained by a pump these results suggest that the major cause of the scintigraphically observed defect was inadequate cellular uptake of 129Cs rather than excessive cellular loss. Since regional myocardial hypoxia produced a reversible defect, scintigraphic studies might overestimate the size of an acute myocardial infarct in man by including the ischemic zone surrounding the infarct.

Displacement correction factor for fast‐neutron dosimetry in a tissue‐equivalent phantom

The displacement correction factor to be used for analysis of fast-neutron dosimetric measurements using air-filled EG and G tissue-equivalent ion chambers in a tissue-equivalent phantom has been investigated using the MANTA neutron radiotherapy beam generated by 35-MeV deuterons on a thick Be target. The displacement correction factor inferred from these measurements is 0.970 for the EG and G IC-17 (1.0-cm3) ion chamber, and is 0.989 for the EG and G IC-18 (0.1-cm3 ion chamber. This multiplicative displacement correction factor has no significant dependence on depth in the phantom or on neutron beam size.

A comparison of two nitroimidazoles and a dihydroquinoline as radiosensitizers and cytotoxic agents

Abstract The search for electron affinic compounds that exhibit the properties needed for a clinically useful hypoxic cell radiosensitizer has led to the setting up of clinical trials with misonidazole, which is a 2-nitroimidazole. Recently, MTDQ a new drug of novel design, a dihydroquinoline (6,6-methylene-bis-2,2,4-trimethyl-1,2-dihydroquinoline)has been synthesized and suggested as a radiosensitizer. The radiosensitizing and cytotoxic properties of misonidazole are compared with MTDQ and a second 2-nitroimadazole Ro-07-0741, which has warranted attention as a possible alternative to misonidazole for clinical use.

Stripping-theory analysis of thick-target neutron production for D+Be (and tissue dose calculation)

The Serber theory for deuteron stripping is employed to predict the shape of the neutron energy spectrum produced by 35 MeV deuterons (D+) on a thick beryllium target. In particular, the observation that the maximum of the neutron energy spectrum (at 0degrees relative to the deuteron beam direction) occurs at approximately 0-4Ed, where Ed is the incident deuteron energy, is explained reasonably well by the calculations. The explanation stems mainly from the fact that the stripping theory for thin targets predicts a narrow maximum at 0-5Ed, and thick target effects shift the maximum downward in energy to approximately 0-4Ed. A number of recent spectral measurements are in agreement with these predictions for a wide range of target materials and incident deuteron energies. The application of this theory also accounts for the previously observed Dd2-99 dependence of the absorbed dose in tissue,per unit charge of D+ ions on target, in the direction of the incident beam. This approximate Ed3 dependence is shown to be a characteristic property of deuteron stripping in a thick target and follows directly from the calculations that predict the neutron energy spectrum.

In vivo activation analysis following neutron therapy in cancer patients

A new mode of local i n v i v oactivation analysis following neutron therapy in cancer patients has been explored at the Naval Research Laboratory Cyclotron Facility. The level of the therapeuticneutron dose administered to a patient presents a unique opportunity to use a Ge(Li) detector to obtain rapidly a high‐resolution γ‐ray spectrum of the activity induced in and around the tumor mass. Methods of analysis and local geometrical effects are discussed.

The light-ion flux mixed with collimated fast-neutron beams

Experimental results are presented which show that neutron beams of the type currently employed in fast-neutron cancer therapy are contaminated by a light ion flux. Tantalum foils were used to demonstrate the existence of the light ions.

Computer generation of dose distributions for a fast-neutron therapy beam

A system has been developed for the computer generation of dose distributions for the MANTA-NRL fast-neutron radiotherapy beam. This program is based on scatter-air ratio (SAR) techniques. A method has been developed to unfold the effect of the neutron-beam profile in the derivation of SARs so that the SARs obtained are those which would be derived if the beam profile were flat. Tables of zero-area tissue-air ratios and SARs are presented. Comparisons of calculated and measured dose distributions are shown. An empirical correction to the usual SAR methods was required to obtain agreement between calculated and measured dose distributions at source-to-skin distances (SSD) which are different from the SSD at which the SAR are derived.

Scattered radiation from a neutron collimator.

Fast-neutron beams are being employed in radiotherapy trials and associated radiobiology studies at numerous centers in the U.S., Europe, and Japan. Since collimated beams of various sizes and shapes are employed, it is desirable to know the composition of the scattered radiation component contributed by the collimator. A simple method is shown for deducing the field composition in terms of a three-component model, from measurements made with three ionization chambers (tissue-equivalent, graphite, and magnesium). The dose contributed by the scattered radiation in the present example was found to be predominantly due to fast neutrons indistinguishable from those in the primary spectrum (from 35-MeV D+ on Be). This method may prove useful for measurements in phantoms as well.