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An ambulatory ventricular function monitor: validation and preliminary clinical results.

A device for the continuous measurement of left ventricular (LV) function was tested in a series of 34 subjects. The instrument consisted of 2 arrays of radiation sensitive cadmium telluride detectors held in place over the region of the left ventricle and lung by a vest-like garment (hence the name VEST). The VEST electronic instrumentation included analog-to-digital converters, a battery pack, microprocessor and gating device, which were worn in a back pack. Data generated by the VEST, including the digitized average electrocardiogram, RR interval, counts/13 ms in each radiation detector, and time since commencement of data recording, were recorded on a cassette tape recorder every 2 minutes for subsequent analysis. At the conclusion of conventional multigated blood pool imaging, the VEST was positioned and worn by the subjects while supine, standing in place and walking. The correlation of ejection fraction calculated independently from the VEST and scintillation camera data was greater than 0.95. The inter-record reproducibility of the ejection fraction measured by the VEST in sedentary subjects was less than 3%.

Ambulatory Care↗

Diagnosis of pheochromocytoma using [123I]-compared with [131I]-metaiodobenzylguanidine scintigraphy.

BACKGROUND: Patient with pheochromocytoma (PCT) cannot be cured without operation, therefore, preoperative determination of the localization of PCT should be performed accurately. [131I]-Metaiodobenzylguanidine (MIBG) scintigraphy is a gold standard for the diagnosis of PCT. However, [123I]-MIBG is also found to accumulate in PCT. In order to clarify the usefulness of [123I]-MIBG scintigraphy for the local detection of PCT, we compared the distribution of [123I]- and [131I]-MIBG in patients with or without PCT. METHODS: [131I]- and [123I]-MIBG scintigraphy was performed in 29 and 16 patients, respectively. In the former group, 14 patients had PCT, 12 had hypertension without any adrenal disorder and three had other diseases. In the latter group, eight patients had PCT, two had hypertension without any adrenal disorder and six had other diseases. The sensitivity, specificity and accuracy of [123I]-compared with [131I]-MIBG scintigraphy were compared. RESULTS: The sensitivity of [131I]- and [123I]-MIBG scintigraphy was 85.7 and 90%, respectively. The specificity of each test was 100%. The accuracy of [131I]- and [123I]-MIBG scintigraphy was 93.1 and 95%, respectively. The quality of images obtained using [123I]-MIBG was better than with [131I]-MIBG, because [123I]-MIBG generated a higher dose of gamma-rays with a higher specificity than [131I]-MIBG. In addition, normal adrenal grands were visualized in 50% of patients tested with [123I]-MIBG scintigraphy. CONCLUSIONS: These results indicate that [123I]-MIBG scintigraphy is a valuable tool for the local detection of PCT, as is [131I]-MIBG scintigraphy. Furthermore, it is possible that [123I]-MIBG can be used as an alternative to [131I]-MIBG for the detection of PCT. Our study was not a prospective study and the background of the patients was not matched. Further prospective studies are needed in order to determine the efficacy of [123I]-MIBG scintigraphy for the diagnosis of PCT.

3-Iodobenzylguanidine↗

Generation and application of monoclonal antibody to human pancreatic carcinoma.

An IgG1 mouse monoclonal antibody (MAb) YPC3 against human pancreatic carcinoma was generated by a hybridoma technique. When human tissue sections were examined with immunohistochemical staining, YPC3 MAb reacted with 28 of 32 (87.5%) cases of pancreatic carcinoma tissue; it failed to react with all 11 cases of normal pancreas examined. When 99mTC-radiolabeled YPC3 MAb was administrated intravenously to the nude mice bearing xenograft of pancreatic carcinoma, clear scintigraphic visualization of tumor xenograft was found with SPECT 24 h after injection. Administration of either YPC3 MAb or LAK cells combined with YPC3 MAb could inhibit the growth of the xenografts in nude mice. These results suggest that YPC3 MAb might be an ideal carrier for radioimmunolocalization and immunotherapy of human pancreatic carcinoma.

Animals↗

Enhanced binding and inertness to dehalogenation of alpha-melanotropic peptides labeled using N-succinimidyl 3-iodobenzoate.

Two peptides of potential utility for targeting melanoma cells, alpha-melanocyte-stimulating hormone (alpha-MSH) and its more potent analogue [Nle4,D-Phe7]-alpha-MSH, were radioiodinated in 45-65% yield using N-succinimidyl 3-[125I]iodobenzoate (SIB). To determine whether this labeling method resulted in improved in vitro and in vivo characteristics, these peptides also were labeled with 131I by direct iodination with the iodogen method. For alpha-MSH, the rapid tissue clearance of both radionuclides in mice was consistent with rapid degradation of the peptide; however, significantly lower levels of 125I were observed in thyroid and stomach, reflecting a greater inertness to deiodination. More extensive comparisons were performed with [Nle4,D-Phe7]-alpha-MSH. The in vitro binding of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH (prepared using SIB) to the murine B-16 melanoma cell line, 34.1 +/- 4.7%, was more than twice as high as that for [Tyr2(131I),Nle4,D-Phe7]-alpha-MSH (15.0 +/- 0.1%), and its KD was more than 10-fold lower than that for conventionally labeled peptide (10 +/- 5 versus 140 +/- 14 pM). The normal tissue clearance of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH in mice was faster than that of [Tyr2(131I),-Nle4,D-Phe7]-alpha-MSH. The 19-40-fold lower activity concentrations of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH in tissues accumulating free iodide (thyroid and stomach) suggest a greater inertness of this peptide to deiodination. The primary urinary catabolite of [Nle4,D-Phe7, Lys11-(125I)IBA]-alpha-MSH was the lysine conjugate of iodobenzoic acid, whereas radioiodide was the chief catabolite generated from [Tyr2(131I),Nle4,D-Phe7]-alpha-MSH. We conclude that further evaluation of [Nle4,D-Phe7,Lys11-(125I)IBA]-alpha-MSH for targeting alpha-MSH receptors is warranted and that SIB may be a useful method for the radioiodination of peptides.

Amino Acid Sequence↗

Quantitative analysis of planar technetium-99m Sestamibi myocardial perfusion images. Clinical application of a modified method for the subtracton of tissue crosstalk.

Application of the Thallium-201 quantitative analysis method to Tc-99m Sestamibi planar myocardial perfusion images results in oversubtraction of tissue crosstalk, defined as 'activity within the myocardial image, which originated outside the heart'. A modified algorithm, specific for Tc-99m Sestamibi, was applied in 60 patients and the results of quantitative analysis to estimate the risk of coronary artery disease were compared with coronary angiographic findings and with visual analysis. New crosstalk planes were generated based on the results in 20 male healthy volunteers. The results in our study group indicate a higher diagnostic accuracy when circumferential profiles are generated on the basis of maximal counts compared to mean counts. Quantitative analysis was able to predict the presence or absence of CAD as accurately as visual analysis. Odds ratios were 1.07 and 1.32 respectively (P < 0.001) for both quantitative maximal uptake and visual uptake analysis. Sensitivity of visual analysis alone was 89%, increasing to 96% with combined visual/quantitative analysis. Specificity of visual analysis decreased from 79% to 64% with combined analysis. Although only minor differences are seen, the maximal count uptake profiles were found to have additional diagnostic value compared to visual analysis alone.

Adult↗

Quantification of walking exercise required for improvement of dipyridamole thallium-201 image quality.

Dipyridamole 201Tl imaging is an accepted diagnostic procedure for the evaluation of patients unable to perform adequate treadmill exercise, but is limited by high infradiaphragmatic activity. While recent studies have shown that the addition of exercise reduces this activity, the amount of exercise needed to effect such an improvement is uncertain. To prospectively evaluate the amount of walking exercise required to produce improvement in image quality, 120 patients were randomized to either a control group receiving dipyridamole alone, or to dipyridamole supplemented with one of four exercise protocols. Ratios of heart-to-liver and heart-to-adjacent infradiaphragmatic activity were generated from anterior images acquired immediately following the test. Heart-to-total infradiaphragmatic activity was also graded semiquantitatively. Results showed improved target-to-background ratios as well as semiquantitative assessment of image quality for dipyridamole supplemented with exercise as compared to dipyridamole alone. No difference was seen between walking in place and Bruce treadmill exercise at Stage 0 or 0.5. A trend towards higher values was seen with Bruce Stage 1 exercise supplementation, but this did not reach statistical significance. No significant complications occurred during the study. We conclude that 3 min of walking exercise is a safe and effective means of improving the quality of dipyridamole 201Tl images.

Adult↗

A molecular approach to immunoscintigraphy: a study of the T-antigen conformation on the surface of tumors.

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both alpha and beta configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the beta configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Animals↗

Teboroxime, sestamibi and thallium-201 as markers of myocardial hypoperfusion: comparison by quantitative dual-isotope autoradiography in rabbits.

The scintigraphic assessment of myocardial hypoperfusion depends on the ability of imaging agents to delineate flow disparities. Accordingly, we compared the differential uptake of teboroxime, sestamibi and 201Tl in normal and hypoperfused myocardium using quantitative dual isotope autoradiography. Rabbits with acute coronary occlusions (n = 29) received dual isotope injections of teboroxime 201Tl or sestamibi 201Tl or single isotope tracer injections. A group of sham-operated controls (n = 15) received teboroxime and/or 201Tl. Multiple 30-mu short axis slices were collected from each heart and mounted on x-ray film along with tissue standards to independently generate separate 99mTc and 201Tl autoradiographs. Teboroxime and sestamibi produced greater normal-to-defect activity contrast than 201Tl in each dual isotope heart (range 8.4-48.9 [teboroxime] versus 2.6-12.3 [201Tl], p < 0.02 and 4.5-10.4 [sestamibi] versus 3.6-7.3 [201Tl], p < 0.03). Similar profiles were obtained in the single isotope hearts. Teboroxime produced larger autoradiographic defects than 201Tl in the dual-isotope hearts [16.0% +/- 5.6% (teboroxime) versus 12.9% +/- 5.3% (201Tl) of the LV, p < 0.02]. We conclude that the 99mTc-based perfusion agents teboroxime and, to a lesser extent, sestamibi, delineate hypoperfused myocardium more clearly than 201Tl. Teboroxime detects the largest area of hypoperfusion and may provide the most accurate assessment of myocardium at risk.

Animals↗

The effect of carrier technetium in the preparation of 99mTc-human serum albumin.

Accumulation of daughter 99Tc in 99Mo-99mTc generator systems may adversely affect the preparation of certain 99mTc radiopharmaceuticals. In a study of the effect of "carrier" technetium on the radiochemical purity of 99mTc-human serum albumin, varying amounts of 99Tc were added to a commercially available electrolytic kit. The maximum amount of 99Tc that could be added to such a kit and still maintain radiochemical purity above 90% was about 3 X 10(15) atoms. When kits containing 10(16) 99Tc atoms were electrolyzed for the conventional 42 sec, the radiochemical purity was only 50.8%. However, when the electrolysis time was varied, it was found that electrolysis for 80 sec yielded a product with greater than 90% radiochemical purity. Four solutions to the problem created by the 99Tc carrier effect are described.

Isotope Labeling↗

Radiation safety precautions for sentinel lymph node procedures.

Radiation safety professionals need guidelines for controlling occupational radiation doses and handling generated contaminated tissues from sentinel lymph node procedures involving 99mTc. Many healthcare facilities do not have formal controls in place, or they adopt policies that may be too restrictive or impractical. During accreditation inspections at healthcare facilities, agencies such as the College of American Pathology and the Joint Commission on the Accreditation of Healthcare Organizations occasionally raise questions about these issues. Inspectors expect to find formal policies to ensure these procedures are performed safely. The objective of this article is to review the basic radiation safety controls needed during sentinel lymph node procedures and to propose guidelines that may be used to control occupational radiation doses and handling of SLN contaminated tissues.

Decontamination↗

Liver and kidney imaging with Ga-68-labeled dihydroxyanthraquinones.

This paper describes the preparation of alizarin (1,2-dihydroxyanthraquinone) and alizarin red S (sodium 1,2-dihydroxyanthraquinone-3-sulfonate) labeled with Ga-68, which is obtained from a new high-yield Ge-68 leads to Ga-68 generator. The uptake of Ga-68 alizarin by liver and spleen RES was studied in rats, dogs, and human, and amounted to 80-85% of the administered dose within 5 min after i.v. injection. Gallium-68 alizarin red S was preferentially accumulated in the renal parenchyma to an extent of 70% within 2 hr after i.v. administration. Both substances combine simple and fast preparation with the potential advantages of positron scintigraphy. Complete labeling of 1 mCi Ga-68 was achieved by 100 micrograms of each compound, amounts that are without any known measurable harm to humans (LD50 alizarin red S for i.v. injected mice = 70 mg/kg (8); LD50 alizarin for i.p. injected mice > 120 mg/kg (18)).

Animals↗

Diagnosis of coronary artery disease by stress echocardiography and perfusion scintigraphy.

This meta-analysis was performed to compare the diagnostic efficacy of stress echocardiography (SE) and Stress perfusion studies (SPS) in detecting coronary artery disease (CAD). A meta-analysis of peer reviewed articles, published in English language, reporting head-to-head comparison of vasodilator stress echocardiography (VSE) and SPS for the diagnosis of CAD, was performed. Data of 13 studies comprising of 860 patients from 13 different institutions were analyzed. Algorithms were developed to generate raw data from published papers to calculate statistical parameters with confidence intervals and then compare them at specified significance levels. The overall diagnostic accuracy of the two tests was almost similar, 0.77 for VSE vs 0.8 for SPS (p=ns). SPS gave higher sensitivity, 0.88 vs 0.70 in cumulative data (p<0.0001) while VSE gave higher specificity, 0.90 vs 0.67 (p<0.0001). Accuracy of VSE with state-of-the-art protocols became even better than SPS (p<0.05). In hypertensive patients specificity of SPS was markedly deteriorated. Contrary to this, VSE gave higher specificity (0.90 vs 0.40) in this subgroup of patients as well. VSE might become an effective alternative of SPS where scintigraphy techniques are not available or affordable.

Coronary Artery Disease↗

Scintigraphic distribution of 123 I labelled proinsulin, split conversion intermediates and insulin in rats.

Insulin, biosynthetic human proinsulin and 2 human proinsulin conversion intermediates, des (64, 65) human proinsulin and des (31, 32) human proinsulin, were labelled with 123 I and the derivatives monosubstituted on Tyr A14 were purified by reverse phase high performance liquid chromatography. The four tracers were injected into anaesthetized rats via a jugular or a portal vein and time activity curves were generated for the liver and kidneys using a gamma camera and an online computer. Liver extraction coefficients varied in the order insulin (38%), des (64, 65) human proinsulin (11.7%), des (31, 32) human proinsulin (3.2%), human proinsulin (1.6%); whereas half-life of hepatic activity varied in the reverse order, from 6 min for insulin, to 45 min for human proinsulin. As expected for a non-receptor mediated process, kidney extraction varied conversely to liver extraction, being highest for human proinsulin and lowest for insulin. It is concluded that the kinetics of human proinsulin conversion intermediates depends upon the site of cleavage and deletion and is intermediate between those of insulin and intact human proinsulin.

Animals↗

The use of diethyl-IDA Tc 99m clearance curves in the differentiation of biliary atresia from other forms of neonatal jaundice.

A family of isotope elimination curves that reflects changes in the biodistribution of diethyl-IDA Tc 99m in neonatal cholestatic jaundice and biliary atresia is defined. Time/activity curves generated from equal areas over the heart and liver were evaluated separately and in conjunction with the scintigraphic data. Patients without scintigraphic evidence of significant hepatic uptake and with a hepatic curve that resembled the cardiac curve were found to have neonatal hepatitis. Good hepatic uptake and a hepatic curve with a terminal portion that appeared to be parallel to or divergent from the cardiac curve were associated with biliary atresia. Apparently converging hepatic and cardiac curves were associated with biliary patency. Although preliminary, these results provide further documentation that diethyl-IDA Tc 99m is useful in discriminating biliary atresia from other causes of cholestatic jaundice, while reducing radiation exposure and the need for pharmacologic intervention.

Bile Ducts↗

Inhalation of pertechnegas: similar clearance from the lungs to that of inhaled pertechnetate aerosol.

It has been reported that the inhalation of pertechnegas (TGO3) generated under an atmosphere of 3% oxygen (O2) in argon (Ar) instead of 100% Ar without O2 in the technegas generator, offers a simple but accurate quantification of clearance from the lungs, permitting it to be used in place of 99Tcm-diethylenetriamine pentaacetic acid (DTPA). The disappearance from the lungs of inhaled TGO3 was so similar to that of inhaled pertechnetate aerosol (TcO4) in this study, that there was neither a statistically significant difference in the clearance half-time (t1/2), nor a difference in the lung images between them. Neither TGO3 nor TcO4 inhalation could distinguish smokers from non-smokers using t1/2. When inhaled, TGO3 appears to behave in a similar manner to TcO4 in the lungs and hence cannot be used in place of 99Tcm-DTPA in clinical practice.

Administration, Inhalation↗

Antiangiogenic therapy for the treatment of pediatric solid malignancies.

Although the past 30 years have seen remarkable progress in the treatment of childhood malignancies, not all types of cancer have enjoyed this improvement in prognosis. Because of this, clinical trials are ongoing in which novel treatment approaches are being evaluated, including immunotherapy, radionuclide therapy, and the use of agents that induce tumor apoptosis or differentiation. Additional treatment strategies are needed, however. One such strategy involves the use of angiogenesis inhibitors. Angiogenesis is the biologic process of new blood vessel formation. In addition to occurring as part of several normal, physiologic processes, angiogenesis is an essential component of a number of pathologic conditions, including cancer. Compelling data suggest that inhibition of angiogenesis can not only prevent tumor-associated neovascularization but also affect tumor growth and spread. An anticancer approach in which the tumor-induced new blood vessels are targeted is particularly appealing for several reasons. First, despite the extreme molecular and phenotypic heterogeneity of human cancer, it is likely that most, if not all, tumor types require neovascularization to achieve their full malignant phenotype. Therefore, antiangiogenic therapy may have broad applicability for the treatment of human cancer, as well as the many other pathologic processes that depend on angiogenesis. Second, the endothelial cells, although rapidly proliferating, are inherently normal with a very low rate of mutation. They are, therefore, unlikely to evolve an angiogenesis inhibitor-insensitive phenotype. This is in distinction to the rapidly proliferating tumor cells that do undergo a high rate of spontaneous mutation and therefore can readily generate drug-resistant clones. This review discusses progress in the development of antiangiogenic therapy for the treatment of pediatric solid tumors.

Angiogenesis Inhibitors↗

Regional tidal volume assessed by gated lung imaging.

We have measured regional lung tidal volumes and functional residual capacities by accumulating and framing iso-volumic images while the patient rebreathes 127Xe. As the lung changes shape during ventilation corrections for changes in geometry were obtained by simultaneous collection of 99Tcm counts from the gated perfusion scan. Regions of interest were made to vary throughout the respiratory cycle so that a region had always the same value of 99Tcm counts. From the corrected 127Xe counts regional tidal volumes (TVr) and functional residual capacities (FRCr) were derived. In patients with established chronic bronchitis and emphysema FRCr were greater and the ratio TVr/FRCr decreased compared with patients with relatively normal static and dynamic lung volumes. Preliminary studies suggest that this ratio was a better discriminator between normal and abnormal regional function than estimates of regional xenon washout. Studies with xenon-133 have contributed to our understanding of the physiology of ventilation but have contributed somewhat less to routine clinical practice. This results in part from the unsatisfactory physical properties of xenon-133. Its relatively low gamma ray energy of 80 keV results in significant self-absorption losses and the activity which may be administered is limited by the radiation dose from the associated beta particles so that relatively poor counting statistics are obtained. With inhaled technetium-99m (99Tcm) microspheres imaging conditions are greatly improved but the distribution of these particles may not equate with the distribution of ventilation particularly if wet particles are used. Moreover, simultaneous microsphere perfusion scans with technetium-99m as a label are impossible. Krypton-81m gas has a suitable energy but the short half-life of the rubidium-81m generator (4.7 h) makes supply difficult and the ultrashort half-life of the krypton-81m gas (13 s) leads to problems in calculating the indices of ventilation. Xenon-127 (127Xe) gas has a more favourable dosimetry profile than xenon-133 because it does not have associated beta particles. Further it has an energy (203 keV) suitable for modern gamma cameras and may be used in the presence of injected 99Tcm microspheres to provide simultaneous ventilation/perfusion imaging. Conventional techniques have assumed that a static image of a dynamic process is adequate. As the lungs move during imaging, some account of this respiratory movement should be made.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intravenous aminohydroxypropylidene bisphosphonate does not modify 99mTc-hydroxymethylene bisphosphonate bone scintigraphy. A prospective study.

Bisphosphonates have marked affinity for bone that makes them useful in both the treatment and imaging of bone lesions. Bone scintigraphy is very sensitive for the detection of bone metastases, which can cause life-threatening hypercalcemia requiring emergency treatment. This prospective study was done to determine whether intravenous administration of pamidronate, a second-generation bisphosphonate used to treat hypercalcemia, affects the affinity of the radiopharmaceutical 99m technetium-labeled hydroxymethylene bisphosphonate (99mTc-HMDP) for bone and bone lesions. Six patients with metastatic bone disease and five with Paget's disease of bone had a 99mTc-HMDP bone scan before and two to four days after an intravenous infusion of pamidronate. The number and activity of metastatic bone lesions were unchanged after pamidronate, even when the second bone scan was done only 24 hours after the pamidronate infusion. Our data suggest that emergency treatment of life-threatening hypercalcemia by intravenous pamidronate does not decrease the sensitivity of subsequent bone scanning done to detect bone metastases.

Aged↗