Vincent J. Sodd

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.

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.

Radiotherapeutic agents: properties, dosimetry, and radiobiologic considerations.

Radioactive nuclides for treatment have occupied an important but somewhat diminishing role in the total practice of nuclear medicine. Although theoretically they should have important potentialities, particularly in the treatment of various forms of cancer, their development in this field has not kept pace with the progress in other treatment modalities in radiation oncology. Indications for the selection of appropriate isotopes for therapy revolve about the emission of beta particles of sufficient energy, which are administered in a chemical form that reaches the tumor. Methods of calculation of doses delivered to sites of deposition are discussed in the text. Radiobiologic considerations include the possibility of early deleterious effects from overdosage, and consideration of chromosomal changes of circulating lymphocytes and their implications. Late effects that have been of great public concern are confined almost solely to possible carcinogenesis, and this effect has been minimal in patients receiving therapeutic levels of radioactive drugs. Genetic and developmental effects, also, have been negligible. Complications encountered more frequently have been leukemia after extensive therapy of thyroid carcinoma, and local fibrosis after direct injection of radioactive colloids into tumor tissue.

Dose to the Metaphyseal Growth Complexes in Children Undergoing 99mTc-EHDP Bone Scans

The spatial temporal distribution of radionuclides in children may differ greatly from that accepted for adults. Following injection of a bone-seeking agent (99mTc-EHDP), radioactivity in the metaphyseal growth complexes of the distal femur and proximal tibia was quantitated in a series of children 4 to 16 years of age, using a gamma camera/computer system. The dose to the growth plate was fount to range from 0.8 to 4.7 rads when adjusted to an administered activity of 200 muCi/kg, compared to approximately 0.6 rad to the adult skeleton for a corresponding study.

Use of Syringe Shields in Clinical Practice

The syringe shield has been available for years but only recently has its use been made mandatory. This study investigates whether use of existing syringe shields in clinical practice would significantly reduce the radiation exposure to laboratory personnel. TLDs were worn on fingers of each hand by the radiopharmacist during preparation and by the physician during injection of 8–10 doses of 15–25 mCi 99mTc for brain scintigraphy. The results showed that physician hand exposure is reduced from 20–80% from the use of syringe shields but the pharmacist exposure reduction is about 50% maximum. The latter results primarily from the additional time required to read the volume accurately through the lead glass window. None of the physicians found the syringe shields to be a problem to the injection procedure, and if the patient experienced any added discomfort, it was not observable. Two conclusions are that syringe shields should be used for injecting high specific activity99mTc, and that the 1 cc shields currently on the market are unsatisfactory for nuclear medicine use.

THE INORGANIC CHEMISTRY OF 99mTc MYOCARDIAL IMAGING AGENTS

A variety of cationic complexes of the general formula [99TcD2X2], where D is a chelating ditertiary arsine or phosphine ligand and X is a halide ligand, have been prepared and characterized by classical chemical techniques. Complexes with D = o-phenylenebis(dimethylarsine) (diars), bis(1,2-diphenylphosphino)ethane (diphos), bis(1,2-diphenylarsino)ethane (dae), and bis(1,2-diphenylphosphino)-ethane (dmpe) have been characterized by single crystal x-ray structural analysis and shown to be trans octahedral complexes of Tc(III). Complexes with D = diars or diphos have been investigated electrochemically and shown to exhibit reversible Tc(III)/Tc(II) couples at biologically accessible potentials. Techniques have been developed to prepare these same complexes using “no-carrier-added” 99mTc rather than 99TC, and resulting [99mTcD2X2]+ cations have been evaluated as potential myocardial imaging agents. In dogs, 99mTc complexes of the diars and dmpe series provide heart images of the same general quality as those obtained with 201Tl, indicating that myocardial muscle contains relatively nonspecific cation acceptance sites that can be probed by a wide variety of cationic agents. In vivo distributions of the [99mTcD2X2] complexes are sensitive to both the nature of D and the nature of X. Considering the large number of cationic 99mTc complexes that can be prepared by varying ligand combinations, it is clear that the optimal 99mTc myocardial imaging agent has not yet been found. Continuing synergistic research in inorganic chemistry and nuclear medicine will be required to fully develop the potential utility of cationic 99mTc radiopharmaceuticals.

Absorbed dose comparison: positron emitters 11C, 13N, and 15O versus gamma-ray emitters.

Absorbed doses were calculated or taken from the literature for various compounds of 11C, 13N, and 15O, and compared to those of presently gamma-ray-emitting nuclear medicine radiopharmaceuticals. As a rule of thumb, the doses per millicurie of the injectable positron-emitting compounds are of the same order of magnitude as the dose per millicurie of 99mTc compounds. The absorbed doses from the injectable positron emitters are nearly one or more orders of magnitude lower on a per millicurie basis than those from the other injectable gamma emitters that were investigated.

THE INORGANIC CHEMISTRY OF 99m Tc MYOCARDIAL IMAGING AGENTS

A variety of cationic complexes of the general formula [99TcD2X2], where D is a chelating ditertiary arsine or phosphine ligand and X is a halide ligand, have been prepared and characterized by classical chemical techniques. Complexes with D = o-phenylenebis(dimethylarsine) (diars), bis(1,2-diphenylphosphino)ethane (diphos), bis(1,2-diphenylarsino)ethane (dae), and bis(1,2-diphenylphosphino)-ethane (dmpe) have been characterized by single crystal x-ray structural analysis and shown to be trans octahedral complexes of Tc(III). Complexes with D = diars or diphos have been investigated electrochemically and shown to exhibit reversible Tc(III)/Tc(II) couples at biologically accessible potentials. Techniques have been developed to prepare these same complexes using “no-carrier-added” 99mTc rather than 99TC, and resulting [99mTcD2X2]+ cations have been evaluated as potential myocardial imaging agents. In dogs, 99mTc complexes of the diars and dmpe series provide heart images of the same general quality as those obtained with 201Tl, indicating that myocardial muscle contains relatively nonspecific cation acceptance sites that can be probed by a wide variety of cationic agents. In vivo distributions of the [99mTcD2X2] complexes are sensitive to both the nature of D and the nature of X. Considering the large number of cationic 99mTc complexes that can be prepared by varying ligand combinations, it is clear that the optimal 99mTc myocardial imaging agent has not yet been found. Continuing synergistic research in inorganic chemistry and nuclear medicine will be required to fully develop the potential utility of cationic 99mTc radiopharmaceuticals.