The uptake of97Ru-transferrin (Ru-TF) in tumor and abscess bearing animals was compared with67Ga-citrate (Ga),123I-transferrin (I-TF), and several other plasma proteins. Maximal concentration in tumor of Ru-TF in mice was three times higher than67Ga-citrate (16.80±4.20 vs 5.08±0.58% D/g) although it occurred later (24 h compared with67Ga which reached its maximum 2 h after injection). Whole body autoradiography (WBARG) with103Ru-transferrin (103Ru-TF) in tumor and abscess bearing rats demonstrated details of the distribution within these lesions. Turpentine-induced abscesses in the rabbits could be visualized with the gamma camera as early as 30 min post-injection of Ru-TF. It seems, therefore, that Ru-TF can be used for tumor and abscess localization. The results indicate that Ru-TF may have some advantages over67Ga-citrate because of the higher concentration in the lesions.123I-transferrin reached a concentration in tumor similar to67Ga (6.89±1.67 vs 5.08±0.58% D/g) but had a very low tumor to blood ratio (0.64). The three compounds investigated (Ru-TF, I-TF and ionic Ga, which binds instantaneously to TF in vivo) have a common lignad, transferrin. It appears, therefore, that tumor affinity is a property of the radionuclide-ligand complex rather than of the radionuclide itself.

Despite advances in video-electroencephalogram (EEG) technology, in many patients distinguishing epileptic seizures from nonepileptic seizures (NES) remains a challenge. Reliable methods to make this distinction are needed. In a pilot study, we performed postictal and interictal single photon emission computed tomography (SPECT) in 22 patients undergoing video-EEG monitoring who had altered responsiveness during an episode. Eleven had seizures, defined as episodes associated with EEG seizure patterns or postictal prolactin (PRL) elevations greater than 1.5 times the highest interictal baseline PRL; 11 had NES. Among the 11 seizures, postictal SPECT was abnormal in seven (regions of hypoperfusion in six and hyperperfusion in one) and normal in four. In six cases (55%), the interictal and postictal SPECT changed. Among the 11 NES cases, postictal SPECT was abnormal in three cases (all hypoperfusion abnormalities) and normal in eight cases. In no case did the interictal and postictal SPECT change. This small sample revealed a trend toward greater hypometabolism (postictal versus interictal) on SPECT for epileptic seizures compared to NES (p < 0.12). There were postictal SPECT changes in two of five seizures unassociated with postictal PRL elevation. Prolactin was elevated in two cases unassociated with change on SPECT. Comparision of postictal to interictal SPECT may help distinguish epileptic seizures from NES. Results from SPECT may also help identify epileptic seizures unassociated with PRL elevation.

The localization of infection sites and of osteomyelitis is still an ongoing diagnostic challenge. In joints affected by arthritis, complicated fractures and around prosthetic devices, three-phase bone scans are non-diagnostic because the underlying condition will cause the third phase scan to be positive, while surrounding soft tissue inflammation may cause the first and second phase scans to be positive as well. Currently, the method of choice in these situations is to use radiolabeled white blood cell scans involving lengthy and expensive procedure and need for delayed imaging. We describe a method using a Tc-99m labeled leukotactic peptide for imaging osteomyelitis and soft tissue infections, which appears to be simpler, and enabling fast diagnosis. Abscesses, clean fractures and infected fractures simulating osteomyelitis were induced in rabbits as described earlier. RMT-1, a tuftsin-mimetic synthetic tetrapeptide labeled with Tc-99m was used. Blood clearance, urine excretion and whole body timed scintigraphy were carried out in normal dogs and evaluation of the compound was performed in dogs and rabbits with soft tissue chemical and bacterial abscesses and in rabbits with clean fractures and experimental osteomyelitis.

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.

Objective: Many different positioning techniques have been attempted in the search for the best method of imaging the breast during scintimammography. A new, effective and comfortable method of positioning the breast is described. Thallium-201-chloride is further explored as an agent to detect breast cancer. Methods: Forty-two women with either a palpable mass or abnormal mammogram were imaged in the lateral decubitus and anterior supine positions. Each patient was injected intravenously with 75–112.5 MBq (2–3 mCi) of 201TI-chloride. Planar images of 10–15 min each were obtained beginning 10 min after injection. Results: Lateral decubitus positioning was very comfortable for the patient and afforded maximum privacy. High-quality images were obtained with breast tissue and axilla clearly visualized. Breast-to-camera distance was minimized to less than 0.5 inch in many cases. The sensitivity of thallium scintimammography was 90% and the specificity was 86% in 26 lesions with pathologic correlation. The smallest lesion detected measured 0.8 cm. Conclusion: Lateral decubitus positioning in scintimammography provides an alternative to prone positioning which is sensitive, comfortable and private. Thallium-201 scintimammography employing lateral decubitus positioning has an acceptable sensitivity and specificity for detecting breast carcinoma.

In his famous work On the Natural Faculties, Galen of Pergamum introduced the idea of [δλκηζ] as the principal mode of kidney function: the attraction of blood to the kidney, he claimed, results in the production of urine [1]. Though unproven in Galen's ancient times and entirely rejected by the later generations as a mechanistic explanation of renal function, the concept of attraction has not only survived, albeit in a modified form, but has become one of the cornerstone principles of modern physiology and our current understanding of the pathophysiology of processes as diverse as platelet aggregation, metastases, immune recognition and wound healing, to name a few, all of which are governed by adhesion molecules. Here we review the role of adhesion molecules in the pathophysiology of tubular obstruction, focusing on the integrins and their newly recognized function in it. The importance of renal tubular obstruction in the pathogenesis of acute renal failure (ARF) was brought to center stage by a series of elegant microdissection studies by Oliver, MacDowell and Tracy [2]. Using servo-null pressure monitoring of the proximal tubular pressure in diverse models of ARF, investigators have provided solid evidence for the elevation in hydrostatic intratubular pressure concomitant with the unchanged stop-flow and estimated glomerular capillary pressures, further confirming the tubulo-obstructive component of this syndrome [3–5]. It has been concluded, therefore, that tubular obstruction and elevated proximal tubular pressure equilibrate glomerular filtration pressure, thus leading to the persisting oliguria. Necrotic epithelial cells have been postulated to provide the matrix for casts obstructing the tubular lumen. Recent findings of viable epithelial cells in the urine of patients and experimental animals with ARF, however, cast doubt on the postulated schema and suggest the possibility of epithelial cell detachment as an important contributor to the development of tubular obstruction [6–8]. In the following discussion we develop this theme, providing data on the possible mechanism(s) of tubular obstruction in ischemic ARF, and on the therapeutic strategies in and benefits of inhibiting tubular obstruction, and suggest some future directions of this fledgling field of investigations.

Whole body timed distribution of pharmacological doses of 14C-cocaine was studied in rats using quanitative 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, pentobartial 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.

The distribution of the racemic mixture of IQNP(1-Azabicyclo [2-2-2] oct-3-yl alpha-hydroxy-alpha-(1-iodo-propen-3-yl)-alpha-phenylacetate), a muscarinic antagonist was described earlier. Recently, the radioiodinated Z and E-(R,R) IQNP isomers have been prepared. Quantitative ARG studies using the Z and E isomers were performed in control rats and after pretreatment with ({plus_minus}) QNB or cocaine. High uptake of (Z)-IQNP was seen in the heart and brain with GI and urinary excretion. Lung uptake was lower than with the racemic IQNP. (Z)-IQNP uptake was maximal at 15 min p.i. with homogeneous distribution in the heart. In the brain, highest uptake was in the caudate, cortex, hippocampus, pons and thalamus. (Z)-IQNP showed higher cerebellar uptake and lower cortical uptake compared to (E)-IQNP. Clearance from brain was slower than bean. Heart and brain uptake of (E)-IQNP were markedly lower than the Z isomer. After QNB pretreatment, almost complete blocking of (Z)-IQNP uptake in heart and brain occurred. Cocaine did not significantly affect the distribution of IQNP. These data indicate that (Z)-IQNP has high affinity for the M2 muscarinic receptor with potential for brain and heart imaging. Cocaine appears to have little effect on the muscarinic-cholinergic receptors in the brain and heart.

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 lixed defects in group 1 (p < 0.01). We conclude that LV enlargement can be easily and reliably determined from routine planar thallium images.

Laminin derived adhesive peptides were studied as potential agents for thrombus specific imaging. Using a novel peptide Tc-99m labeling method studies were performed in vitro using human whole blood clots and platelets, and in vivo scintigraphy in animals with experimental thrombi. Aliquots of 0.1 ml human blood were placed in inclined Petri dishes until clot was well formed. Clots were rinsed 3x with phosphate buffer and 10 {mu}Ci Tc-99m YIGSR II was added. After incubation at room temperature for 1 hr, clots were again washed 3x. Residual activity was measured. Platelets were harvested using routine methods and incubated with Tc-99m YIGSR II, washed and assayed. Blocking experiments using cold YIGSR II showed that the Tc-99m labeled peptide preparation YIGSR II binds specifically and selectively to clot and platelets as compared to control experiments using nonspecific human Tc-99m IgG. Tissue distribution studies showed rapid blood clearance, urinary excretion and to a lesser degree GI tract excretion. Tc-99m YIGSR II was lower in all organs except kidneys compared to Tc-99m 50 H.19, Tc-99m IgG and Tc-99m YIGSR I. Tc-99m-YIGSR II consistently visualized thrombi within 30 min p.i. In vivo scintigraphic (thrombus/contralateral side) ratio was 3:1 and ex vivo direct counting (thrombosed tomore » nonthrombosed vessel segment) was 5.4: 1. Compared to monoclonal antibodies peptide preparations are non- or minimally immunogenic, preparation is probably less expensive and there is also less danger of viral DNA contamination. These considerations and our data indicate that the Tc-99m-YIGSR II peptide has significant potential as a thrombus imaging agent.« less

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.

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.

Radionuclide ventriculography was used to measure global and regional diastolic relaxation and filling in normal subjects (NL), patients with left anterior descending coronary disease (LAD), and patients with prior anterior wall myocardial infarctions (AWMI). The isovolumic relaxation period (IVRP) was identified as the interval between end systole and the start of fast filling. The peak filling rate (PRF) was used to quantitate left ventricular filling. The purpose was to test the ability of regional and global isovolumic relaxation periods to identify patients with coronary artery disease and to explore the relationship between left ventricular relaxation and filling. The global IVRP was prolonged to a similar extent in LAD and AWMI patients when compared to normal subjects (NL +/- 54.6 +/- 7.9 msec; LAD = 105.6 +/- 14.8 msec; AWMI 133 +/- 9.5 msec; p < 0.001). The anteroseptal regional IVRP was also prolonged in LAD and AWMI patients (N = 47.5 +/- 8.3 msec; LAD = 142.8 +/- 15.3 msec; AWMI = 150.9 +/- 10.9 msec; p < 0.001). The posterior wall IVRP was similar in the three study groups. A prolonged regional anteroseptal IVRP identified 73% of LAD patients and 92% of AWMI patients. No relationship was found between left ventricular global or regional isovolumic relaxation and left ventricular filling. Thus, prolonged global and regional IVRP's obtained from resting radionuclide ventriculograms can identify patients with coronary artery disease. In this group of patients, left ventricular relaxation and filling were not related.