Harold A. O'Brien

Relation between regional myocardial uptake of rubidium-82 and perfusion: absolute reduction of cation uptake in ischemia.

Experiments were undertaken using rubidium-82 and position tomography to examine the relation between myocardial perfusion and cation uptake during acute ischemia. Rubidium-82 was repeatedly eluted from a strontium-82-rubidium-82 generator. In six dogs emission tomograms were used to measure the delivered arterial and myocardial concentrations at rest and after coronary stenosis, stress and ischemia. There was a poor overall relation between regional myocardial uptake and flow measured by microspheres and a large individual variability. Extraction of rubidium-82 was inversely related to flow. Significant regional reduction of cation uptake was detected in the tomograms when regional flow decreased by more than 35 percent. This reduction was significantly greater when ischemia was present. A small but significantly greater when ischemia was present. A small but significant decrease (33.0 +/- 9.1 percent, mean +/- standard deviation) in the myocardial uptake of rubidium-82 was detected only when flow was increased by more than 120 percent in relation to a control area after administration of dypiridamole. The technique using rubidum-82 and tomography was applied in five volunteers and five patients with angina pectoris and coronary artery disease. Myocardial tomograms recorded at rest and after exercise in the volunteers showed homogeneous uptake of cation in reproducible and repeatable scans. In contrast, the patients with coronary artery disease showed an absolute mean decrease of 36 +/- 14 percent in regional myocardial uptake of rubidium-82 after exercise. These abnormalities persisted in serial tomograms for more than 20 minutes after the symptoms and electrocardiographic signs of ischemia.

Character of transient ischemia in angina pectoris

There is growing interest in the possible therapeutic and prognostic significance of silent myocardial ischemia in coronary artery disease (CAD) and its detection by ambulatory electrocardiographic (ECG) monitoring. In 100 apparently healthy normal subjects (20 with angiographically normal coronary arteries), Holter monitoring revealed significant ST-segment depression in only 2 (both over 40 years, one with positive treadmill test, the other with risk factor for CAD). No significant ECG changes were found in those with normal coronary vessels. In 30 patients with documented CAD, significant ST-segment depression during 1,934 episodes over 446 days of monitoring over 18 months was found. Only 24% of the episodes were associated with angina. Asymptomatic and symptomatic episodes were associated with comparable changes in perfusion detected by positron emission tomography. Heart rate increases greater than 10 beats/min preceding the onset of the ST-segment changes occurred in only 23% of the episodes. There was considerable variability in the ST-segment changes in the same patient monitored serially over long periods of time. The data indicate that it is extremely uncommon for patients without CAD to exhibit silent myocardial ischemia, whereas patients with stable angina exhibit frequent, variable and often asymptomatic ECG evidence of myocardial ischemia rarely triggered by increases in heart rate. These findings are likely to be of therapeutic and prognostic significance.

Serum stability of 67Cu chelates: Comparison with 111In and 57Co☆

Simple chelates and chelate conjugated monoclonal antibodies labeled with 111In, 57Co and 67Cu demonstrate marked differences in stability when exposed to a serum environment. Among these radiometals, on DTPA, the order of stability is 111In greater than 57Co much greater than 67Cu. On benzyl-EDTA, the order of stability is 111In congruent to 57Co much greater than 67Cu. Among those investigated, the only serum stable 67Cu chelate found was 67Cu-TETA. The order of stability observed for 57Co vs 67Cu is contrary to published equilibrium constants. These in vitro studies suggest that the in vivo behavior of metal chelates exposed to a complex molecular environment may not be predicted by classically determined equilibrium constants.

Medium-energy spallation cross sections. 1. RbBr irradiation with 800-MeV protons

Radiochemical and instrumental methods have been used to measure the production cross sections of 40 spallation products induced in RbBr targets by 800-MeV protons. RbBr is irradiated at LAMPF to produce the following isotopes for use in diagnostic nuclear medicine: 75Se—(67±2)mb; 72Se—(12±0.4)mb; 68Ge—(19±1)mb; 67Ga—(41±1)mb; 62Zn—(2±1)mb; 67Cu—(1.6±0.08)mb.

The production and recovery of 77Br at Los Alamos for nuclear medicine studies

Abstract A procedure for the synthesis and isolation of 77 Br for nuclear medicine research has been developed at LASL. Metallic Mo targets are irradiated at LAMPF with medium-energy protons at high beam current. Following dissolution, volatilization, precipitation, and ion exchange techniques, 77 Br is recovered with a (91±7)% chemical yield and is completely free of all other radioactive species with the exception of small levels of 76 Br and 82 Br. Ci-quantity production capabilities have been demonstrated, and the product is proving successful for the labelling of diverse radiopharmaceuticals. Future improvements in the process are also discussed.

The isolation of 82Sr from 200 to 600 MeV proton-irradiated Mo targets for biomedical applications

Abstract 82 Sr is of interest in nuclear medicine as the generator of its short-lived daughter, 82 Rb. Experimentation has begun at the Clinton P. Anderson Meson Physics Facility, and spallation reactions have been induced in Mo targets with 200–600 MeV protons to produce microcurie amounts of a variety of radionuclides. A six-step radiochemical procedure, incorporating precipitation, solvent extraction, and ion exchange techniques, has been developed for the separation and purification of Sr radioactivities from other spallation products and the bulk target material. γ-Ray spectrometry was used for isotope characterization, and chemical yields of ten different spallation-induced radioelements were determined for this analytical scheme. Radiostrontium can be quantitatively recovered in a sufficiently decontaminated state for use in biomedical generator development, and this procedure is being scaled up to a hot cell operation for actual production irradiations.

Preparation and evaluation of a hydrous tin(IV) oxide 82Sr/82Rb medical generator system for continuous elution

Hydrous tin(IV) dioxide in the Na+-form appears to be the most efficient inorganic exchanger for a reliable and versatile clinical 82Rb generator. Continuous elution with a commercial physiological NaCl solution yields 82Rb ranging between 10 and 40% at a flow rate as low as 3 to 10 mL/min respectively. At the same time the Sr breakthrough is less than 1.6 10(-6)%/mL. A clinical generator loaded with 100 mCi 82Sr (150 mCi 85Sr) and continuously eluted for 3 min at a typical flow rate of 5 mL/min yields 40 mCi of 82Rb, 8 nCi of 82Sr and 11 nCi of 85Sr. The total absorbed radiation dose for 40 mCi 82Rb administered is primarily due to 82Rb and has been estimated for the three principal target organs as 760 mrad for the kidneys, 520 mrad for the heartwalls and 276 mrad for the lungs. The 82,85Sr contribution to the dosimetry has been shown to be negligible. The absence of radiolysis with generators loaded with high level of 82Sr was demonstrated by the excellent reproductibility of continuous elution properties of the generator during its practical shelf-life estimated to 5-6 weeks of clinical use which would require more than 30 L of eluent.

Interlaboratory comparison of spallation-reaction cross sections for iron and copper with 590-MeV protons☆

Abstract Three sets of thin foils of carbon, aluminum, iron and copper have been simultaneously irradiated with 590-MeV protons. Cross sections of some of the γ-ray emitting spallation products from Fe and Cu have been measured independently by members of the three participating laboratories. The results are compared and average cross sections are given. Various sources of error common to such experiments are presented, and the steps taken to minimize them in this work are discussed.

Transfer of copper from metallothionein to nonmetallothionein proteins in cultured cells

Copper uptake and distribution with time among cytoplasmic proteins were followed in cultured cells under several conditions: (1) CHO cells, which cannot synthesize metallothioneins, were labeled with67Cu in the presence of 100 μM ZnCl2; (2) Cdr30F9 cells, which contain some constitutive metallothionein (MT), were labeled in the absence of additional ZnCl2 and; (3) Cdr30F9 cells were labeled in the presence of ZnCl2, under which conditions they synthesized additional metallothioneins. The exogenous67Cu and ZnCl2, where present, were then removed, and the distributions of67Cu among size fractions of the cellular proteins were observed at intervals for 16 h. In addition, a culture identical to condition (3) above was also treated with 100 μM ZnCl2 during the redistribution period. The67Cu was initially resolved into three peaks by Sephadex G-75 chromatography: high molecular weight, intermediate molecular weight, and MT. The67Cu in the MT fraction decreased with at1/2 of 10–12 h. In contrast to this, generally, in cells with a higher initial67Cu bound to metallothionein, there was a progressive increase in the amount of67Cu eluting with the high- and intermediate-molecular-weight fractions. Since no other source of67Cu was available, these experiments suggest that copper stored in MT can be transferred to other proteins in these cells.

First use of millicurie levels of172Hf−172Lu in the industrial sector

The first use of the172Hf−172Lu generator system in industry is reported. Millicurie quantities of172Lu have been utilized for radiotracer studies of oil pipeline flow rates, refinery column residence times, and the performance of a coal liquefaction pilot plant.