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We have developed a method of labeling biologically active labile macromolecules, such as human fibrinogen (HF) and anticardiac-myosin Fab (AM-Fab), with Tc-99m at neutral pH. This method uses dithionite reduction of pertechnetate and subsequent labeling, to test the method with acid-labile macromolecules. Complexes of diethylene triamine pentaacetic acid with macromolecules such as human fibrinogen (D-HF) and anticardiac-myosin Fab (D-AM-Fab) were labeled and utilized in in vitro and in vivo studies. In biodistribution studies, the Tc-99m D-HF had a two-component blood clearance (half-times 1 hr and 15 hr) and was 80--88% coagulable. The Tc-99m AM-Fab retained its immunoreactivity as tested by affinity chromatography; also during in vivo localization in experimental myocardial infarction. This labeling technique provides an easy and efficient approach to the Tc-99m labeling of other biologically active and acid-labile macromolecules.

The ability to diagnose and localize vascular graft infections has been a major challenge. Recent studies in animal models and humans with focal bacterial infection have shown that radiolabeled, polyclonal, human immunoglobulin G accumulates at the site of inflammation and can serve as the basis for an imaging technique. This study investigated this new technique for the diagnosis and localization of vascular graft infections. Twenty-five patients with suspected vascular infections involving grafts (22), atherosclerotic aneurysms (2), and subclavian vein thrombophlebitis (1) were studied. Gamma camera images of the suspected area were obtained between 5 and 48 hours after intravenous administration of 1.5 to 2.0 mCi (56 to 74 mBq) of indium 111-labeled, human, polyclonal immunoglobulin G. Scan results were interpreted without clinical information about the patient and were subsequently correlated with surgical findings, other imaging modalities, and/or clinical follow-up. In 10 of 10 patients found to have positive scan results, localized infections were confirmed at the involved sites. In 14 of 15 patients whose scan results were interpreted as negative, no vascular infections were identified at follow-up. The patient with false-negative results and recurrent bacteremia from an aortoduodenal fistula was found to have a negative scan outcome at a time when his disease was quiescent. These data suggest that nonspecific, human, indium 111-labeled immunoglobulin G scanning can be a useful noninvasive means of localizing vascular infections.

The clinical significance of anterior precordial ST segment depression during acute inferior myocardial infarction was evaluated in 67 consecutive patients early after onset of symptoms with gated blood pool scans, thallium-201 perfusion images, and 12-lead ECGs. Patients with anterior ST depression (n = 33) had depressed mean values for left ventricular ejection fraction (54 +/- 2% [mean +/- S.E.M.] vs 59 +/- 2%; p = 0.02), cardiac index (3.1 +/- 0.2 vs 3.6 +/- 0.2 L/m2; p = 0.03), and ratio of systolic blood pressure to end-systolic volume (2.0 +/- 0.1 vs 2.5 +/- 0.3 mm Hg/ml; p = 0.04) compared to patients with no anterior ST depression (n = 34). Patients with anterior ST depression had (1) lower mean wall motion values for the inferior, apical, and inferior posterolateral segments (p less than 0.05) and (2) greater reductions in thallium-201 uptake in the inferior and posterolateral regions (p less than 0.05). However, anterior and septal (1) wall motion and (2) thallium-201 uptake were similar in patients with and without ST depression. Thus, anterior precordial ST segment depression in patients with acute inferior wall myocardial infarction represents more than a reciprocal electrical phenomenon. It identifies patients with more severe wall motion impairment and greater hypoperfusion of the inferior and adjacent segments. The poorer global left ventricular function in these patients is a result of more extensive inferior infarction and not of remote septal or anterior injury.

To evaluate the severity of coronary artery disease in patients with severe peripheral vascular disease requiring operation, we performed preoperative dipyridamole-thallium imaging in 54 stable patients with suspected coronary artery disease. Of the 54 patients, 48 had peripheral vascular surgery as scheduled without coronary angiography, of whom 8 (17 per cent) had postoperative cardiac ischemic events. The occurrence of these eight cardiac events could not have been predicted preoperatively by any clinical factors but did correlate with the presence of thallium redistribution. Eight of 16 patients with thallium redistribution had cardiac events, whereas there were no such events in 32 patients whose thallium scan either was normal or showed only persistent defects (P less than 0.0001). Six other patients also had thallium redistribution but underwent coronary angiography before vascular surgery. All had severe multivessel coronary artery disease, and four underwent coronary bypass surgery followed by uncomplicated peripheral vascular surgery. These data suggest that patients without thallium redistribution are at a low risk for postoperative ischemic events and may proceed to have vascular surgery. Patients with redistribution have a high incidence of postoperative ischemic events and should be considered for preoperative coronary angiography and myocardial revascularization in an effort to avoid postoperative myocardial ischemia and to improve survival. Dipyridamole-thallium imaging is superior to clinical assessment and is safer and less expensive than coronary angiography for the determination of cardiac risk.

Using a bifunctional chelating agent, indium-111 was attached to a monoclonal antibody 10- 3D2 , specific for a 126-kilodalton phosphoglycoprotein antigen associated with human mammary carcinoma, and was then used to localize and visualize human mammary tumors hosted in nude mice. Simultaneous tumor concentration of In-111-10- 3D2 was eight times greater than that of control I-125-MOPC-21. Uptake of F(ab')2 and Fab of 10- 3D2 was also compared. the scintigrams demonstrated that intact antibody provided the best images. Control In-111-labeled MOPC-21 and plasma did not show specific localization in the tumor. Uptake of In-111-labeled 10- 3D2 was also compared in two lines of human mammary tumors, BT-20 and HS- 578T . Imaging with 10- 3D2 was better for BT-20 than for HS- 578T . These studies demonstrated that (a) In-111-10- 3D2 can be utilized to image human mammary tumors hosted in nude mice; (b) intact antibody provided the best tumor images, although F(ab')2 had optimal target-to-background ratios for earlier imaging; and (c) different mammary tumor lines with possibly different concentrations of tumor-associated antigen showed different rates of uptake and apparent saturation with 10- 3D2 .

The utility of nonspecific polyclonal IgG for external imaging of experimental atherosclerosis was tested in a series of rabbits after balloon catheter deendothelialization of the abdominal aorta. Following injection of 111In-IgG, 111In-Fc, or 111In-Fab serial images were recorded. In addition, several animals received 125I-low density lipoproteins [125I-LDL], or 125I human serum albumin [125I-HSA] as positive and negative controls. Forty-eight hours after injection of the radiolabeled proteins, the aortas were removed, divided into abdominal and thoracic regions, counted, and autoradiographed. The images acquired after injection of 111In-IgG and 111In-Fc, showed clear focal accumulation of radioactivity in the healing abdominal aorta. In contrast, the images obtained after injection of 111In-Fab did not show focal radionuclide accumulation. For 111In-IgG and 111In-Fc there were three to six times as many counts in the abdominal as in the thoracic aorta, while for 111In-Fab and 125I HSA, the abdominal and thoracic counts were nearly equal. The results suggest that radiolabeled IgG and Fc can be used to image experimental atherosclerosis.

A technique for the semiautomatic calculation of left ventricular volumes from multigated blood-pool tomograms (MGBPT) was tested in a series of 12 patients undergoing contrast ventriculography within 48 hr of gated tomography. The parameters necessary for the calculation of volume were developed in a chest phantom study performed with a series of 99mTc-filled balloons representing the right and left ventricles. The images were analyzed for volume using a percentage of peak count-threshold of the left ventricular balloon. This technique resulted in a correlation of r = 0.99 of the calculated to the true phantom volumes (y = 0.87x + 27.4, p less than 0.01, s.e.e. = 7.87 ml). The patient studies were recorded at 16 frames/cardiac cycle at each of 60 angles over a 360 degree rotation. Reconstructed data were presented in an endless loop cine format producing a set of sequential "beating tomographic slices" in the transverse, apical four-chamber, short-axis, and long-axis oblique views. Measurements of end systolic volume (y = 0.79x + 30, r = 0.93, p less than 0.001, s.e.e. = 24 ml), end-diastolic volume (y = 0.63x + 60, r = 0.94, p less than 0.0001, s.e.e. = 20 ml) and ejection fraction (y = 0.88x - 0.02, r = 0.92, p less than 0.001, s.e.e. = 0.08) determined from the semiautomated volume method correlated well with those determined by left ventricular contrast angiography. A qualitative comparison of MGBPT, planar imaging, and left ventricular angiography in 12 patients revealed that the visual assessment of wall motion using the 16-frame tomographic slices had significant advantages over planar and single plane angiographic data in the identification of inferior, basal, and septal wall motion abnormalities as well as the extent of involvement by aneurysm formation. A quantitative comparison of wall motion in the long-axis oblique view of the MGBPT to the RAO 30 degree ventriculogram (y = 0.74x + 8.7, r = 0.82, p less than 0.0001, s.e.e. = 14%) confirmed the qualitative similarity of these two views. We conclude that MGBPT is promising as a method for accurately measuring left ventricular volumes and assessing regional wall motion.

A national survey was conducted to examine the extent of adoption and use of nuclear imaging procedures in cardiology in hospitals by 1979 and to develop estimates for 1983. The data are based on the responses of 171 hospitals from a representative 200-hospital sample stratified for region, bed-size, and teaching status. Extrapolating the data, it is estimated that 2,106 hospitals nationally use cardiac nuclear imaging. In 1979, hospitals with at least 200 beds performed an estimated 396,000 cardiac nuclear imaging studies at a cost of $93 million. By 1983, it is estimated that 4,061 hospitals had the capability to perform cardiac nuclear imaging and that national expenditures would exceed $200 million ( noninflated dollars). Although cardiac nuclear imaging procedures have been demonstrated to be valuable in detecting coronary artery disease or measuring ventricular function, these procedures were rapidly being adopted by the medical community at a time when only limited information about their effectiveness and efficiency are available.

To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether damaged arterial wall selectively accumulates lipoproteins, normocholesterolemic rabbits were injected with human radiolabeled low density lipoproteins, high density lipoproteins, and/or albumin 24 hr to 12 weeks after balloon-catheter de-endothelialization of the abdominal aorta. When 125I-labeled low density lipoproteins and 99mTc-labeled albumin were injected simultaneously, the amount of 125I-low density lipoprotein present 24 hr later in abdominal aortas increased steadily, for several weeks, above the amount present at 24 hr in control animals. The increase correlated closely with the degree of re-endothelialization and correlated closely with the degree of re-endothelialization and reached an average maximum for the whole abdominal aorta of three times control when re-endothelialization was between 75 and 85% complete. By contrast, the amounts of 99mTc-albumin or 125I-labeled high density lipoprotein in balloon-damaged abdominal aortas, and the amounts of 125I-low density lipoprotein, 125I-high density lipoprotein, or 99mTc-albumin in undamaged thoracic aortas of injured animals showed no such increase. As early as 2 weeks after de-endothelialization, en face radioautographs made following injection of 125I-labeled low density lipoproteins revealed localized areas of greatest radioactivity around the leading edges of regenerating endothelial islands, broad areas of intermediate radioactivity corresponding to the de-endothelialized areas, and very like radioactivity in the re-endothelialized areas. This pattern occurred rarely with 125I-labeled high density lipoproteins and not at all with 125I-labeled albumin. The results suggest that low density lipoproteins are selectively accumulated by the healing rabbit aorta and that the accumulation is greatest in regions where the endothelium is actively regenerating.

Two cases are reported in which combined radionuclide imaging using gated cardiac blood pool scintigraphy and /sup 67/Ga-citrate scintigraphy aided in evaluating lymphomatous involvement of the heart and distinguishing tumor involvement from other cardiac disorders.