R.Edward Coleman

Indium-111 labeled platelets: Studies on preparation and evaluation of in vitro and in vivo functions

Abstract Platelets have been labeled with a lipid soluble complex of the radionuclide indium-111. The complex is formed with 8-hydroxyquinoline and extracted in chloroform which is then evaporated to dryness. The residue is dissolved in 50 μl of ethanol and diluted to 200 μl with normal saline. Platelets are separated by differential centrifugation, washed and suspended either in Tyrodes-albumin solution or in normal saline. The solution of 111 In-complex is added to separated platelets and more than 95% of the radioactivity is incorporated with the platelets. The function of the labeled platelets has been studied by their aggregability using adenosine diphosphate and collagen as the stimulating agents. No adverse effects have been observed. The survival of the indium-labeled platelets was similar to that observed with chromium-51 labeled platelets. Labeled canine platelets have been administered to dogs in whom venous thrombi had been induced by alteration of the intima by an electric current. The thrombi were detected by imaging 50 minutes after administration of the labeled platelets. Twenty-four hours later the thrombi were removed and had 20–50 times the radioactivity of an equal weight of blood. Accumulation of large amounts of radioactivity in surgical wounds has also been observed. Damage of the intima of carotid arteries in animals by a balloon catheter demonstrated 8 to 20 times more activity in the damaged artery than in the normal artery. Results indicate that In-111 labeled platelets have potential both for platelet survival studies and for evaluation of vascular damage.

Indium-111 labeled leukocytes in the evaluation of suspected abdominal abscesses

Sixty-eight indium-111-labeled leukocyte imaging studies were performed in 53 patients with suspected abdominal abscesses. Twenty-nine studies gave abnoramal results. Nine wound infections were demonstrated, and 14 abscesses were correctly identified. Four studied demonstrated colonic accumulation, one of which remains unexplained, and two accessory spleens were identified. Indium-111 leukocyte imaging is a sensitive and specific study in evaluating patients with suspected abdominal abscess. Differentiation of abscess from other causes of inflammation has not been a problem. The exact role of leukocyte imaging compared with gallium-67 citrate imaging, ultrasound and computerized tomography remains to be determined.

Improved detection of myocardial infarction with technetium-99m stannous pyrophosphate and serum MB creatine phosphokinase

The relative sensitivity and combined value of myocardial technetium-99m stannous pyrophosphate imaging and determinations of serum MB creatine phosphokinase (the myocardial CPK isoenzyme) in detecting acute myocardial infarction were evaluated in 41 patients with suspected infarction and 23 patients recovering from cardiac surgery. In the patients with suspected infarction, myocardial infarction was confirmed in 25 and was consistently associated with increased serum MB CPK. Abnormal radionuclide images were obtained in 23 of 25 patients (92 percent) with definite myocardial infarction and in 2 of 16 patients without confirmed infarction. Although the localization of infarction by imaging correlated well with the localization by electrocardiogram, infarct size estimated by imaging did not correlate well with estimates based on peak total serum CPK activity or serial changes in CPK activity. Serum MB CPK activity increased after cardiac surgery in 6 patients undergoing valve replacement and in 17 patients undergoing coronary arterial bypass surgery. However, no patient with valve replacement and only 1 of the 17 with bypass surgery had an abnormal radionuclide image. These results suggest that (1) abnormal radionuclide images in patients without infarction can be distinguished from abnormal images indicative of ischemic necrosis by consideration of MB CPK activity and (2) interpretation of elevated MB CPK activity, particularly in particularly in patients undergoing cardiac surgery, is facilitated by evaluation with imaging.

Mechanisms Contributing to Myocardial Accumulation of Technetium-99m Stannous Pyrophosphate After Coronary Arterial Occlusion

The relation between the accumulation of pyrophosphate and technetium-99m in myocardium with reversible and irreversible ischmic injury was studied in dogs subjected to transitory or persistent coronary arterial occlusion. Among four dogs with coronary occlusion maintained for less than 20 minutes, none had either increased MB creatine kinase (CK) (the myocardial CK isoenzyme) activity serum or a positive 99mTc stannous pyrophosphate image. Seven dogs with coronary occlusion maintained for 30 or more minutes had elevated serum MB CK activity, and five of the seven had positive (abnormal) images. Thus, although false negative images may occur occasionally despite myocardial damage, both increased serum MB CK and abnormal images generally accompanied prolonged coronary occlusion. In contrast, ischemia without infarction was not associated with abnormal images. Both 99mTc and 32P labeled pyrophosphate were accumulated extensively and proportionally in myocardium from zones of infarction, and uptake of both tracers was comparable although modest in isolated mitochondria. Similar results were obtained after myocardial infarction in animals with induced profound leukopenia. Thus, phagocytosis of the radiopharmaceutical agent by leukocytes migrating into the infarct is not an essential mechanism accounting for uptake. These results indicate that abnormal images reflect uptake of pyrophosphate, associated with 99mTc, by irreversibly injured myocardium rather than leukocytic infiltration involved in the inflammatory response in the heart.

Imaging of the inflammatory response in ischemic canine myocardium with 111indium-labeled leukocytes

Myocardial leukocyte infiltration is one hallmark of acute myocardial infarction. In order to detect noninvasively this inflammatory response associated with acute myocardial infarction, we produced coronary occlusion in eight dogs, intravenously administered autologously labeled indium-111 (111In) leukocytes and scintigraphically monitored accumulation of radionuclide in myocardium. Seventy-two hours after coronary occlusion, 111In-labeled white cells accumulated in regions corresponding to myocardial infarcts, and positive images with 111In-labeled leukocytes correlated well with images obtained with technetium-99m pyrophosphate and computer-reconstructed tomograms obtained with nitrogen-13-labeled ammonia. In contrast, two control dogs subjected to sham operation did not exhibit positive 111In-leukocyte images. Scintigraphic results with 111In-labeled leukocytes were verified in vitro by analysis of radioactivity in normal myocardium and in infarcts. Thus, leukocytic infiltration associated with acute myocardial infarction can be detected noninvasively in vivo.

Technetium-99m stannous pyrophosphate scintigrams in normal subjects, patients with exercise-induced ischemia and patients with a calcified valve

Although technetium-99m stannous (99mTc[Sn]) pyrophosphate has been shown to be a specific and sensitive index of myocardial infarction, abnormal images have been reported in patients with unstable angina or ventricular aneurysm. Sixty-one subjects--33 patients subjected to maximal treadmill stress testing, 23 normal subjects and 5 patients with a calcified aortic or mitral valve--underwent imaging with 99mTc(Sn) pyrophosphate to determine whether abnormal images are associated with (1) exercise-induced ischemia, (2) delayed clearance of tracer from the blood pool, or (3) calcified intracardiac structures. Myocardial injury was excluded on the basis of normal MB creatine kinase (CK) values in all patients with stress testing. All eight patients with an abnormal exercise stress test had normal images. Four of 25 patients with a normal exercise stress test had diffusely abnormal images. In some normal subjects diffusely abnormal images were present 60 minutes after injection of the tracer, but became normal 90 to 120 minutes after injection. Variations in clearance of tracer from the blood pool were noted in this group. Patients with a calcified aortic or mitral valve had normal images. We conclude that (1) exercise-induced ischemia is not associated with abnormal 99mTC(SN) pyrophosphate images; (2) images are not necessarily abnormal in patients with a calcified valve; and (3) delayed removal of tracer from the cardiac blood pool may result in diffusely abnormal images even in normal subjects; in these cases, repeat images should be obtained at least 2 hours after injection of the tracer to avoid false abnormal images.

Effect of iodination level on the properties of radioiodinated fibrinogen

Abstract The effect of iodination level on the biological clearance of radioiodinated fibrinogen was investigated. Canine, human and rabbit fibrinogen were included in the study to also test for possible differences among various species. Iodination of fibrinogen with 3 to 9 iodine atoms/molecule resulted in essentially unchanged isotopic clottability as compared to preparations at the conventional level of 0.5 iodine atom/molecule. No changes in molecular size due to covalent aggregation were observed by SDS gel electrophoresis with radioiodinated human fibrinogen preparations. Canine and human fibrinogen iodinated with up to 4.5 iodine atoms/molecule exhibited little change in biological clearance behavior relative to the conventional iodination level. However, rabbit fibrinogen iodinated with 3.5 iodine atoms/molecule displayed a difference in clearance when compared to the 0.5 iodine atom/molecule preparations. Thus, canine and human fibrinogen can be iodinated with 4.5 iodine atoms/molecule without altering their biological clearance behavior while rabbit fibrinogen is more sensitive to this iodination level.

Brain Scanning in Cerebral Vascular Disease: A Reappraisal

The frequency of abnormal brain scans in patients with cerebral vascular disease admitted to a stroke intensive care unit has been evaluated in relation to diagnosis, time after onset of symptoms, effect of delayed imaging and the degree of clinical neurological recovery. In patients with completed thromboembolic infarction, 33% had abnormal scans including 39% of those with hemispheric lesions and 14% with posterior fossa lesions. Completed hemorrhagic infarction occurred in seven patients, and three (43%) had abnormal brain scans. Of 14 patients with either transient ischemic attacks or reversible ischemic neurological deficit, two (14%) had abnormal scans. Twenty-seven percent of brain scans in patients with completed thromboembolic infarction were abnormal in the first two days after infarction, a higher frequency than previously reported. Delayed images confirmed the initial interpretation that the scan was either normal or abnormal in 71% of the cases while in 10% of the cases only the delayed views were abnormal. The frequency of abnormal scans was significantly greater in patients who died or had a large neurological deficit at discharge than in patients with lesser residual deficit.

123I-labeled soluble fibrin: preparation and comparison with other thrombus imaging agents.

Abstract Radioiodinated soluble fibrin, a derivative of radioiodinated fibrinogen, has been investigated for thrombus localization. Soluble fibrin can be labeled with 123 I as the radionuclide for imaging thrombi with a scintillation camera. Protein iodination grade 123 I is produced by a distillation and extraction procedure from the product of the 121 Sb ( α , 2 n ) 123 I reaction in the Washington University 54-in. cyclotron. Labeling with these 123 I preparation is effected by the iodine monochloride method. Induced 4–6-hr-old femoral vein thrombi in dogs can be visualized beginning 2 hr after injection of 1 mCi of 123 I-labeled soluble fibrin. This new radiopharmaceutical may be useful for imaging actively-propagating thrombi in patients, especially in areas of large blood pool. Its potential appears to be similar to that of 123 I-labeled highly iodinated fibrinogen, another new thrombus imaging agent.

Radionuclides in the assessment of myocardial infarction

Radionuclides in Cardiology have been used mainly for detection of myocardial infarction’ and assessment of left ventricular function.2 The need for improved detection of myocardial infarction is related to the lack of sensitivity and specificity of the ECG or plasma enzymes in certain clinical conditions.“, a Diagnosis of infarction after cardiac surgery is particularly troublesome since even creatine phosphokinase isoenzymes, specific for myocardial damage, are consistently elevated as a result of the iatrogenic injury., The recent interest in protection of ischemic myocardium6 requires measurement of infarct size and several studies suggest that quantification of infarct images may be possible,‘, 8 which has intensified the search for more appropriate radionuclidesg Four categories of radionuclides have been utilized to identify zones of h (2) metabolic substrates (labeled free fatty acids, 13NH,15; (3) inert gases (s5Kr, *%e)l6,1’; and (4) labeled microspheres or macroaggregates.18, I9 However, radionuclides which accumulate in areas of infarction (“hot