Radiolabeling brachytherapy sources with Re-188 through chelating microfilms: stents.

Rhenium-188 (Re-188, T(1/2) = 17 h) emits beta particles (E(max) = 2. 12 MeV) having an ideal range for intravascular brachytherapy and certain cancer brachytherapies. Re-188 was attached to metal wafers and stents via a chelating microfilm, and these brachytherapy sources characterized in vitro and in vivo. To prepare the sources, a siloxane film containing reactive amines was plasma deposited on the metal, a chelating microfilm conjugated to the amines, and the chelating microfilm used to attach Re-188. Re-188 was selectively bound to materials coated with the chelating microfilm. Binding correlated with the amount of radionuclide used. Wafers (1 cm(2)) bound up to 62.9 MBq (1.7 mCi) of Re-188 with yields generally near 30%. Stents bound up to 26.6 MBq (720 microCi). Typically, stents were labeled to bind 4-12 MBq and deposit 10-30 Gy at 2 mm in the arterial wall. In phantom studies, the longer nitinol stents deposited doses of 2.3 Gy/MBq (0.085 Gy/microCi), while shorter stainless steel stents deposited 4.62 Gy/MBq (0.171 Gy/microCi). After placement in arteries of pigs, only the Re-188-stents were detected by scintigraphy at times up to 24 h. Scintigraphy did not detect activity in other organs. Blood sampling (0.1-24 h) detected maximum radioactivity (up to 388 cpm/mL/100micro Ci) at 6 h. We conclude that on-demand radiolabeling of stents and other brachytherapy sources with Re-188 can be performed routinely.

Enhanced external counterpulsation as an adjunct to revascularization in unstable angina.

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for chronic stable angina. Despite intensive risk factor modification, a patient required two surgical coronary revascularizations and seven multivessel angioplasties over a 26-month period, demonstrating recurrent unstable angina and persistent thallium perfusion defects despite revascularization. Post EECP, angina was relieved, thallium defects were resolved and the patient has remained asymptomatic for 36 months.

Improved exercise tolerance following enhanced external counterpulsation: cardiac or peripheral effect?

The effect of treatment with enhanced external counterpulsation (EECP) on exercise hemodynamics and myocardial stress perfusion in 27 patients with chronic stable angina was studied. A majority (22/27 or 81%) of patients improved their exercise tolerance after EECP treatment, and a similar percentage (21/27 or 78%) of patients improved their radionuclide stress perfusion images. Post-EECP maximal exercise heart rate and blood pressure, while demonstrating a linear relation with exercise duration, did not increase significantly despite the increased exercise duration. This suggests that the increase in exercise duration after treatment with EECP is due to both improved myocardial perfusion and altered exercise hemodynamics. EECP therapy thus appears to exert a "training' effect, decreasing peripheral vascular resistance and the heart rate response to exercise. Coronary disease patients may improve their exercise tolerance after EECP because of both improved myocardial perfusion and a decrease in cardiac work load.

Quantitative autoradiographic measurement of cocaine-induced regional myocardial metabolic changes in hypertensive rats.

A rat model of hypertensive cardiomyopathy was studied to evaluate the acute effects of cocaine on the myocardium. Using autoradiographic microimaging techniques, myocardial perfusion (201Tl) and energy substrate utilization (glucose: [14C]2-fluoro-2-deoxy-D-glucose-[14C]2DG and fatty acid (15-[p-iodophenyl])-3-R,S-methyl pentadecanoic acid-[131I]BMIPP) were studied in Dahl strain salt-sensitive normotensive and hypertensive rats with and without intravenous cocaine. The right ventricle, septum, endocardium and epicardium of the left ventricle were analyzed. Increased perfusion (18%) was seen in the myocardium of the hypertensive rats as compared to the normotensive rats. There was higher [14C]2DG (254%) and lower fatty acid (13.2%) uptake in the hypertensive rats, indicative of a shift from aerobic to anaerobic substrate utilization. In cocaine-treated normotensive rats, a generalized decrease in myocardial perfusion (30%) and increased glucose metabolism (89%) was seen. In cocaine-treated hypertensive rats, the increased myocardial perfusion (16%) was heterogeneous and was more pronounced in septum and epicardium. The endocardium and epicardium in the hypertensive rats showed an overall increase (23%) in glucose utilization after cocaine which was not as dramatic as was seen in the normotensive heart and a slight increase in fatty acid utilization. These results are consistent with prior observations that under pressure overload the myocardium responds non-uniformly. It may well be that the hypertensive cardiomyopathic heart is unable to respond to the challenge of cocaine by further increasing glucose utilization. These data obtained in an animal model of hypertension seem to indicate that hypertension may increase the risk of cardiac complications related to cocaine.

Spatial and temporal distribution of cocaine and effects of pharmacological interventions: wholebody autoradiographic microimaging studies.

Whole body timed distribution of pharmacological doses of 14C-cocaine was studied in rats using quantitative autoradiographic microimaging. Rapid, intense uptake was seen in the brain, spinal cord, adrenals and nuchal brown fat pad. Clearance of cocaine was fastest from the cerebellum. Cortex activity reached soft tissue activity within 20 min. Uptake in the heart and adrenals was very intense following the same time course as in the brain. Kidney activity increased gradually at the same time as in the liver, probably representing specific binding as well as an excretory pathway of cocaine. Desipramine decreased uptake in the heart and adrenals and a piperazine derivative (GBR 12909) caused decreased uptake in the brain, heart and adrenals. Scopolamine, pentobarbital and cold cocaine caused decreased uptake in all organs and increased uptake (excretion) in the liver. Thus, cocaine appears to bind in the brain to the dopamine transporter and to a lesser extent to transporters for norepinephrine and serotonin. In the heart cocaine binds to norepinephrine, serotonin and dopamine. The targeting of cocaine to specific organs and the time sequence correspond to the pharmacological effects of cocaine.

Assessment of left ventricular enlargement from planar thallium-201 images.

Although a subjective assessment of left ventricular (LV) size can be made from planar thallium images, the validity of this practice had not been critically assessed. The objective of this study was to determine the accuracy of planar thallium imaging in the assessment of LV size by using two-dimensional guided M-mode echocardiographic measurements as the standard. Consecutive patients (n = 100) who had clinically indicated stress thallium and echocardiography done within a time interval of 1 month were selected. LV size was classified as dilated or normal on immediate and 4-hour-delayed thallium scans by the consensus of two blinded observers. When present, perfusion defects were noted. LV end-diastolic internal diameter (LVIDd) was measured on M-mode images. The mean LVIDd was 5.7 cm in patients with dilated LVs compared with 5.0 cm in those with normal LVs (p < 0.01). By using an LVIDd of 5.6 cm as the upper limit of normal, the sensitivity and specificity of planar thallium imaging for detection of left ventricle enlargement were 87% and 86%, respectively. Corresponding positive and negative predictive accuracies in this population were 65% and 96%, respectively. There was a higher incidence of fixed defects in group 1 (p < 0.01). We conclude that LV enlargement can be easily and reliably determined from routine planar thallium images.

Abscess scintigraphy with 99mTc-human immunoglobulin (IgG) using a one-step labeling method.

It was shown earlier that non-specific human gamma globulin (IgG) labeled with 111In can be used as an agent for abscess localization. We describe experimental results with 99mTc-IgG in animals bearing abscesses and tumors using a one-step labeling method with 99mTc. We studied this compound in several animal models: mice bearing turpentine abscesses and subcutaneously transplanted sarcomas, in rats with turpentine or E. coli abscesses and intracerebrally implanted gliomas and in rabbits with E. coli or turpentine abscesses. Blood clearance was studied in dogs. It was found that the absolute concentration of 111In-IgG in abscess and tumor was higher than that of 99mTc-IgG. However, the abscess-to-tumor ratio was higher for 99mTc-IgG. The 99mTc-IgG images were of high quality and abscesses could be detected as early as 30 min post-injection (p.i.). It appears that 99mTc-IgG has many potential advantages over 111In-IgG because of better physical properties of 99mTc, simpler preparation, lower cost and greater availability and the possibility of using higher 99mTc doses.

Brain imaging of an alcoholic with MRI, SPECT, and PET.

A medically healthy chronic alcoholic without evidence of neurological and neuropsychological impairment was studied with magnetic resonance imaging (MRI), single photon emission computerized tomography (SPECT), and positron emission tomography (PET). An age-matched normal volunteer was evaluated with the same scans for comparison. The MRI of the alcoholic revealed prominent ventricles and mild cortical atrophy. SPECT and PET revealed predominant involvement of the frontal cortex as shown by decreased frontal blood flow and metabolism. This case illustrates the sensitivity of brain imaging techniques in detecting cerebral abnormalities even in the absence of neurologic and/or neuropsychological impairments.

Imaging of cocaine-induced global and regional myocardial ischemia.

Severe and often fatal cardiac complications have been reported in cocaine users with narrowed coronary arteries caused by atherosclerosis as well as in young adults with normal coronaries. We have found that in normal dogs cocaine induces severe temporary hypoperfusion of the left ventricle as indicated by a significantly lower 201Tl concentration compared to the baseline state. The most significant decrease in uptake occurred 5 min after injection and was more pronounced in the septal and apical segments. Following intravenous administration of cocaine, instead of gradual disappearance of 201Tl from the left ventricle, there was continuous increase in 201Tl concentration in the left ventricle. These imaging experiments indicate that the deleterious effects of cocaine on the heart are probably due to spasm of the coronaries and decreased myocardial perfusion. Since spasm of the large subpericardial vessels does not seem to explain the magnitude of the increased coronary resistance and decreased coronary flow after cocaine as described in the literature, it is suggested that microvascular spasm of smaller vessels plays a major role in the temporary decrease in perfusion. The data may also suggest that severe temporary myocardial ischemia is probably the initiating factor for the cardiac complications induced by cocaine.

A monoclonal antibody reacting with platelets for monitoring thrombolysis.

Thrombus immunoscintigraphy with radiolabeled monoclonal antibodies are presently undergoing intense clinical evaluations. Reports on clinical trials of radiolabeled antifibrins are very encouraging and results of antiplatelet antibody evaluations are forthcoming. Animal studies with antiplatelet antibodies indicate that a diagnosis can be made within the critical "lytic window" of 4-6 h, and thus the imaging procedure may be used as an adjunct to thrombolytic therapy, i.e. screening of patients. We now report on a potentially new application of monoclonal antibodies, immunoimaging for monitoring thrombolysis. In vitro studies were performed with "standardized clots" incubated with 99mTc 50H.19 and re-incubated with streptokinase (SK), urokinase (UK) or recombinant tissue plasminogen activator (rt-PA). The decrease in clot-bound 99mTc 50H.19 activity after SK, UK or rt-PA incubation was proportional to the decrease in clot weight (r = 0.90-0.98). The direct effects of these thrombolytic agents on the labeled antibody and the possible interference of aspirin, warfarin and heparin in thrombus immunoimaging were also investigated. Aspirin, heparin and warfarin did not interfere with clot-binding of 99mTc 50H.19. Thrombolytic agents did not affect the stability of the radiolabel or immunoreactivity of 50H.19. These results indicate that 99mTc 50H.19 is a promising agent that may enable monitoring thrombolysis in addition to thrombus immunoimaging.

The scintigraphic pattern of renal angiomyolipoma.

The patterns of renal and gallium scintigraphy in a patient with renal angiomyolipoma are presented. Renal study with Tc-99m DTPA demonstrated a photopenic area in the flow and delayed images. Ga-67 citrate imaging did not show any evidence of increased activity. Although this pattern is also seen in renal cysts, scintigraphy seems to be valuable in the evaluation of angiomyolipoma. It helps differentiate it from renal carcinoma or renal abscess (which may be gallium avid), especially when the tumor is characterized by a paucity of adipose tissue and complicated by hemorrhage, in which case CT and ultrasonographic patterns are not diagnostic.