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PubMed1997

Modulation of the multidrug resistance P-glycoprotein: detection with technetium-99m-sestamibi in vivo.

UNLABELLED: Overexpression of the multidrug resistance (MDR1) P-glycoprotein (Pgp) has been documented in nearly all forms of human cancers and increased levels of Pgp in some tumors correlate with poor response to treatment. Technetium-99m-sestamibi has recently been validated as a Pgp transport substrate. Pgp is also normally expressed along the biliary canalicular surface of hepatocytes and the luminal side of proximal tubule cells in the kidney, while not expressed in heart. METHODS: Focused on these organs with known Pgp status, we present the findings on 99mTc-sestamibi scintigraphy of three patients with refractory cancer who were imaged before and after administration of SDZ PSC 833, a second-generation, high-potency modulator of Pgp. RESULTS: Before treatment with SDZ PSC 833, scintigraphy using 99mTc-sestamibi showed normal, prompt clearance of the radiotracer from the liver and kidneys relative to the heart. After administration of the Pgp modulator, 99mTc-sestamibi was selectively retained in the liver and kidneys. CONCLUSION: Hepatobiliary and renal clearance of 99mTc-sestamibi are Pgp-mediated, and inhibition of Pgp transport in these organs can be successfully imaged using 99mTc-sestamibi in patients. Similar results might be expected with this and related radiopharmaceuticals for functional imaging of Pgp transport and modulation in tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1983

Location of metastatic breast carcinoma by a monoclonal antibody chelate labelled with indium-111.

The ability of a radiolabelled monoclonal antibody, LICR-LON-M8 (M8), to locate metastatic breast carcinomas has been investigated. The scans generated by M8, either when labelled with radioiodine, or when conjugated with diethylenetriamine-pentaacetic acid (DTPA) and labelled with radioactive indium (111In), have been compared with X-rays and 99mTc-methyl diphosphonate (MDP) bone scans. All 10 patients with skeletal metastases had positive 111In-DTPA-M8 scans and the overall correlation with X-rays and MDP scans was good but varied with the region studied. By contrast, radioiodinated M8 did not detect metastases at any site. The discrepancies between 111In-DTPA-M8 images and conventional techniques may be related to the different stages in the evolution and development of the lesion at which the various techniques detect bone metastases.

Antibodies, Monoclonal↗
PubMed1994

The computer-generated bone marrow subtraction image: a valuable adjunct to combined In-111 WBC/Tc-99m in sulfur colloid scintigraphy for musculoskeletal infection.

In-111 WBC scintigraphy supplemented by visual comparison with concurrent Tc-99m SC bone marrow imaging is used to identify infection within the marrow-containing skeleton. This retrospective study demonstrates the value of the computer-generated WBC/SC bone marrow subtraction image. Thirty-one patients with various conditions (postsurgery with or without orthopedic hardware, bacteremia with persistent fever, joint arthroplasty, and miscellaneous) underwent combined WBC/SC with bone marrow subtraction imaging. Infection was present in 21 of 36 possible sites (14 osseous, 7 soft tissue; 8 acute, 13 chronic). The bone marrow subtraction image identified two of these sites, which were not appreciated by visual inspection. The sensitivity, specificity, and accuracy for bone marrow subtraction were 95%, 93%, and 94%, respectively, as compared to 86%, 93%, and 89%, respectively, for the visual assessment of WBC and SC images. Computer-assisted subtraction imaging improves overall accuracy and enhances diagnostic certainty of combined WBC/SC scintigraphy for infection in the marrow-containing skeleton.

Adult↗
PubMed1993

Experimentally produced pulmonary arterial occlusion in the dog: identification with pertechnegas inhalation.

Pertechnegas, a variant of technegas, is a fine, dry aerosol formed when technetium-99m pertechnetate is vaporized in a technegas generator under appropriate conditions. After inhalation, the aerosol is deposited almost entirely on the surfaces of terminal respiratory structures. Unlike technegas, however, pertechnegas crosses the alveolar-capillary membrane and leaves the lung through the pulmonary circulation. To demonstrate prolonged retention of pertechnegas in regions of lung supplied by an occluded pulmonary artery, 12 pulmonary arterial occlusions were experimentally produced in two dogs. After inhalation of pertechnegas, a transient focus of increased pulmonary radioactivity was seen in 11 occlusions; 10 of these 11 foci were easily confirmed by means of subsequent perfusion scintigraphy. All 11 foci of retained pertechnegas corresponded to the location of the non-perfused lung. Thus, it is possible to identify ischemic lung with focal retention of pertechnegas (a finding that indicates preserved ventilation but diminished perfusion) by use of a single examination.

Aerosols↗
PubMed1990

Mucociliary clearance and transport in bronchiectasis: global and regional assessment.

Global and regional mucociliary clearance and transport in the lungs was studied in 20 patients with bronchiectasis by radioaerosol inhalation lung cine-scintigraphy and the quantitative analysis following inhalation of ultrasonically-generated 99mTc-tagged human serum albumin aerosol (mass median diameter; 1.93 microns with geometric s.d. of 1.52). In bronchiectatic lung regions, deposition of inhaled aerosol was diminished or inhomogeneous. Transport of inhaled radioactivity from the bronchiectatic regions was deranged in 95% of the patients (19/20). The following abnormal mucous transport patterns were regionally observed; stasis in 12 of the 20 patients (12/20), regurgitation or reversed transport in 14/20, straying in 8/20, spiral or zigzag transport in 1/20, and/or various combinations of these four abnormal transport patterns. When coughs occurred, regurgitation and stray became more marked in the bronchiectatic regions. These regional abnormalities in mucociliary transport seem to be responsible for the development of infections and hemoptysis in the bronchiectatic regions.

Administration, Inhalation↗
PubMed1986

Reliability of dietary Ca and P levels and bone mineral content as predictors of bone mechanical properties at various time periods in growing swine.

Seventy-two growing pigs were fed one of nine dietary treatments that provided a range of Ca (0.4%-1.2%) and P (0.4%-1.2%) levels arranged in a two-factor central composite design. Two pigs per treatment after either 5 (T5) or 10 (T10) wk and four pigs per treatment after 15 (T15) wk were slaughtered, and the femur (F) and third (MT3) and fourth (MT4) metatarsal bones were collected for evaluation of mechanical properties (force, stress and modulus of elasticity), ash weight (ASHW), percent ash (PASH) and bone mineral content (BMC) using photon absorptiometry. Stepwise regression analysis utilized to generate best-fit equations predicted that dietary Ca and P levels could reliably predict force (R2 = 0.83), ASHW (R2 = 0.93) and BMC (R2 = 0.89) of the MT3 bones but the prediction of force differed at the various time periods. Stress (R2 = 0.41), the modulus of elasticity (R2 = 0.29) and PASH (R2 = 0.17) were not reliably predicted by dietary mineral levels. The amount of force withstood by the MT3 bone could be reliably predicted by BMC (R2 = 0.90), but stress was not reliably predicted by BMC (R2 = 0.40) even if dietary Ca levels were considered. These results indicated that dietary Ca levels between 0.6% and 1.2% and dietary P levels between 0.6% and 0.8% did not adversely affect growth, efficiency or bone development. The BMC, as determined by photon absorptiometry, was not a reliable predictor of bone strength.

Animals↗
PubMed1975

Peripheral arteriography an overview of its origins and present status.

Within a month after Roentgen's discovery of the X-ray, the first cadaveric peripheral arteriogram was performed. It was not until 28 years later that the initial in vivo femoral arteriogram was reported. Arteriographic growth and development since that time have been punctuated with such names as Seldinger, Steinberg, Viamonte, Abrams, Sones, and many more. Keeping pace with their technical and diagnostic achievements has been the cause for a whole new industrial field - that of angiographic equipment and technology. New X-ray tubes, generators, film, etc. have been developed. Angiographic tables are available which have been designed to do highly subspecialized studies. The spectrum of catheter curves and materials available allows visualization of vessels down to the order of 0.1 mm when combined with magnification. Chemoangiography for treatment and subselective venous sampling for hormonal assays are commonplace. Although "the beginnings" for all angiography lie in the evaluation of peripheral vasculature, equipment sophistication for this basic study has often lagged behind that of the more glamorous organal examinations. The development of the biphasic ijection technique hopefully represents an anwer to both multiple injections and X-ray exposures. It allows single injection and single exposure visualization of the vascular tree from distal aorta to the pedal vessels.

Angiography↗
PubMed2000

Radiation effects in lymphocytes of children living in a Chernobyl contaminated region of Belarus.

PURPOSE: To investigate cytogenetic and mutational effects in lymphocytes from individuals chronically exposed to radiation from the Chernobyl catastrophe. MATERIALS AND METHODS: Nine years after the Chernobyl accident (1986), peripheral blood lymphocytes from 20 Kalinkovichi children (age 10-15) and 10 Minsk children (age 10-17) were analysed for genetic damage by several assays. Radiation damage in exposed children was investigated in descendants of progenitor cells that were irradiated during a short period immediately after the accident. In the time-span between the accident and blood sampling the cells were also irradiated chronically by internal radiation originating from ingested radionuclides and, to a smaller extent, by external radiation from radionuclides. The parameters measured in whole blood smears were the frequency of micronucleated mononucleated lymphocytes and binucleated lymphocytes with nucleoplasmic bridges and associated micronuclei. Cultures of cytokinesis-blocked lymphocytes were used to analyse mononuclear and binuclear cells for the presence of micronuclei, also cell killing effects. A colony assay was used to study induction of recessive mutations in the HPRT gene. RESULTS: The analysis of whole-blood smears indicated a doubling of the frequency of micronuclei per 100 mononuclear lymphocytes in exposed children compared with unirradiated children. Small numbers of binucleated lymphocytes with nucleoplasmic bridges and associated micronuclei were found in blood smears from exposed children. Analysis of cytokinesis-blocked cultures indicated in mononuclear cells of exposed children a statistically significant increase in the frequency of micronuclei. When the same parameters were studied in binucleated cells there was no difference between exposed and unexposed children. Results of the dye-exclusion assay showed a four-fold increase in the percentage of dead cells between exposed and unexposed children. There was no evidence for induction of HPRT mutations in exposed children. CONCLUSION: These results indicate that the frequently advocated procedure of simply analysing micronuclei in cytokinesis-blocked binucleated lymphocytes can result in an underestimate of genetic damage induced by radiation accidents. Biodosimetric studies should therefore employ a battery of assays for the detection of several types of genetic damage in different generations of lymphocytes.

Adolescent↗
PubMed1986

Thallium circumferential profiles in the detection of coronary artery disease--assessment by receiver operating characteristic curve analysis.

Thallium uptake and redistribution in the myocardium was quantitated using circumferential activity profiles. The profiles were determined from images in the LAO 35, LAO 70 and anterior views, obtained after peak exercise and after 3-4 h redistribution. A retention curve was constructed from these profiles, displaying the redistribution profile as a fraction of the stress profile. Normal values were obtained from 21 normal patients and compared to the images from 68 patients suspected of having coronary artery disease (CAD). Of the latter, 20 had normal/non-significant CAD and 48 had 70% or greater stenosis of one or more vessels on coronary angiography. Several methodological variations were examined: calculation of the profiles using the peak or average counts around the ventricle, uniform or interpolative background subtraction, normalisation of the profiles to their peak or mean counts. Receiver operating characteristic (ROC) curves were generated for profiles calculated using these variations and compared with the ROC curves obtained by visual interpretation of both analogue and computer-enhanced images by two experienced observers. The uniform background subtraction method was found to be better than the interpolative method, and normalisation to the mean of each curve was preferable to normalisation to the peak. ROC curves using profiles calculated using the peak myocardial counts were identical to the ROC curves from profiles using the average counts, but the operating points on the two curves differed. Computer enhancement of the digital images resulted in increased sensitivity for CAD without loss of specificity when compared to the interpretation of the analogue images. The circumferential profiles were found to provide a further increase in sensitivity and were highly reproducible.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Difference in inhaled aerosol deposition patterns in the lungs due to three different sized aerosols.

Deposition patterns of inhaled aerosol in the lungs were studied in five normal subjects and 20 patients with lung disease by inhaling radioaerosols with three different particle size distributions. These aerosols were generated from BARC, UltraVent, and Mistogen-EN-142. Particle size distributions generated by these three nebulizers were 0.84, 1.04 and 1.93 microns in activity median aerodynamic diameter (AMAD) with its geometric standard deviation (sigma g) of 1.73, 1.71 and 1.52, respectively. Deposition patterns of inhaled aerosols were compared qualitatively and quantitatively by studying six different parameters: alveolar deposition ratio (ALDR), Xmax, Xmean, standard deviation (S.D.), skewness and kurtosis of the radioactive distribution in the lungs following inhalation. It has been found that aerosol deposition patterns varied with particle size. The unevenness of aerosol deposition, Xmax, Xmean and the number of 'hot spots' became more prominent with the increase in particle size, whereas values of ALDR and S.D. decreased as particle size increased. Knowing these deposition characteristics would facilitate a judicious application of aerosol inhalation to medical use.

Administration, Inhalation↗
PubMedDate not supplied

Evaluation of transplanted hepatocytes using HIDA scintigraphy.

BACKGROUND: Hepatocyte transplantation has generated interest because of potential clinical application in enzyme deficiency disorders and acute hepatic failure. Ex-vivo HIDA scintigraphy has been used to assess graft survival after hepatocyte transplantation. The present study evaluates in-vivo99mTc-HIDA scintigraphy to assess graft function after hepatocyte transplantation. METHODS: Rat hepatocytes were isolated by a modified collagenase digestion technique and injected intrasplenically into 6 syngenic rats; 4 control rats received intrasplenic saline injections. In-vivo HIDA scintigraphy and histological evaluation were done 90 days after transplantation. RESULTS: Five of the six rats in the study group showed prompt and progressive accumulation of HIDA in the spleen. Histological examination showed presence of hepatocytes in the splenic red pulp. None of the control group animals had splenic uptake of HIDA. CONCLUSION: HIDA scintigraphy may be a useful modality for assessment of graft function after intrasplenic hepatocyte transplantation.

Animals↗
PubMedDate not supplied

Determination of self-absorption corrections for gamma analysis of environmental samples: comparing gamma-absorption curves and spiked matrix-matched samples.

Accurate determination of the massic activity of gamma-emitting radionuclides in environmental samples, particularly sediments and soils, cannot be achieved without taking into account sample self-absorption. The extent of self-absorption in the sample will depend on a number of factors including sample composition, density, sample size and gamma-ray energy. The preferred method for correcting for this effect is to use spiked or natural matrix reference materials that match each sample type to be analysed. However, for laboratories that must measure a wide variety of sample matrices this method is too costly and time-consuming. Another technique commonly used is to make direct gamma-ray transmission measurements for each sample. This method, while more practical, still requires a minimum of three measurements to be made for each sample analysed. A more convenient method is to prepare sets of gamma-absorption curves. This approach involves making a series of direct transmission measurements for samples of varying densities but similar type. Sets of matching samples, both spiked and unspiked, were prepared and density correction factors determined using the direct transmission method and the spiked sample approach. It was found that, for soil and sediment samples, these two methods typically differed by 5-9% for higher energy gamma rays and by 12-15% for the 59.54 keV 241Am peak. Gamma-absorption curves were also derived and, for the admittedly limited dataset, 95% confidence intervals of +/-7% for the curve generated using the spiked samples method were obtained.

Calibration↗
PubMed1981

Scintigraphic evaluation and dynamic studies with thallium-201 in thyroid lesions with suspected cancer.

Scintigraphic studies of the thyroid with thallium-201 chloride were performed in 46 patients in whom the final diagnosis was established by histology. In dynamic studies of 36 patients, sequential imaging was performed the first 40 min after injection. A single exponential, Cexp(-lambda t), was fitted to each of the curves generated from apparently pathological and from normal regions in each patient, as determined by earlier conventional scintigrams. To minimize the effects of normal individual variations, the relation between pathological (p) and normal (n) regions in the same patient was emphasized and quantified by two parameters, namely the extrapolated zero-time intercept (Cp/Cn) and the time development (lambda p-lambda n) of the ratio of counting rates/unit area in the two regions. The turnover appears to be somewhat slower for pathological tissue than for normal tissue. Although this difference was significant on the 5% level for both cancer and adenoma as a group, only the relative disappearance rate (lambda p-lambda n) resolved cancer frm adenoma and from goiter on the same level. All but one of the differentiated cancers had an increased uptake.

Adenocarcinoma↗
PubMed1984

Fourier amplitude and phase analysis in the clinical evaluation of patients with cardiomyopathy.

Fifty-four patients with a cardiomyopathy were studied by RNCA and Fourier amplitude and phase image analysis. The study group included patients with ischemic cardiomyopathy (27) and an equal number of patients with a primary cardiomyopathy: drug-induced (22), idiopathic (three), radiation-induced (one), and amyloidosis (one). Twenty-eight patients had rest studies alone and 26 had both rest and stress studies (80 total). The mean rest LVEF in the ischemic group was 27.9%, in the drug-induced group 36.5%, and in the idiopathic group 30%. The stress LVEF decreased in 92% of patients with ischemic cardiomyopathy and 45% of patients with primary (drug-induced) cardiomyopathy. Fourier amplitude and phase images were generated for each study. Amplitude and phase images were abnormal in all patients with an ischemic cardiomyopathy. LV amplitude abnormalities were regional and phase was directional. A zone of dysynergy on phase analysis was present in 44% of patients with ischemic cardiomyopathy. In the drug-induced primary cardiomyopathy group, all patients had abnormal amplitude and 86% had abnormal phase. Amplitude abnormalities were global rather than regional and phase patterns were nondirectional. Only one patient had a zone of dysynergy on the phase image. We conclude that the stress LVEF alone cannot consistently differentiate between ischemic and primary cardiomyopathies and that Fourier amplitude and phase analysis may be useful in determining the etiology of a cardiomyopathy (ischemic vs primary).

Adolescent↗
PubMed1992

Dual radioisotopic study: a technique for the evaluation of vasculogenic impotence.

Arterial and venous systems are the main points for the evaluation of vasculogenic impotence. To evaluate both of these systems in the same study we propose a dual radioisotopic study in which 99mtechnetium (99mTc) and 133xenon (133Xe) were used. The changes in 99mTc and 133Xe radioactivities administered intravenously and intracavernously, respectively, were monitored before and after intracavernous papaverine injection. These changes were determined as time activity curves, which were generated from the region of interest over the penis. A 99mTc penogram index derived from the 99mTc time activity curve was significantly different in the control and arteriogenic impotence groups (131.67 +/- 74.6 versus 62.94 +/- 51.6, p less than 0.01). A meaningful correlation between 99mTc penogram index results and duplex ultrasonographic findings were observed (r = 0.905). 133Xe penogram index, derived from the 133Xe washout curve was significantly different in the control and venogenic impotence groups (-25.65 +/- 24.9 versus -56.09 +/- 13.4, p less than 0.01). Also, a meaningful correlation was obtained between pharmacocavernosometry and 133Xe penogram index results of venogenic impotent patients (r = 0.86). These findings suggest that the dual radioisotopic study will be a useful technique in the evaluation of the entire vascular system of the penis, since it is a noninvasive method.

Adult↗
PubMed1991

An improved method for the quantification of left-to-right cardiac shunts.

We have investigated a technique for quantifying QP/QS in left-to-right cardiac shunts. In this method, the gamma variate, which is fitted to the first-pass portion of the lung curve, is used to generate a curve, which simulates the response of a normal lung curve with systemic recirculation. The difference between this curve and the observed lung curve is then used to calculate QP/QS. This method was evaluated on a set of simulated lung time-activity curves with precisely known QP/QS values on a group of 11 patients with no clinical suspicion of cardiac shunt and on a group of 30 patients referred for cardiac shunt studies. The QP/QS in each of these studies was determined by three individuals using both the Maltz-Treves method and the new method. This method yielded QP/QS values that were more accurate on the simulated lung data and had less interobserver variation on all the studies than those obtained from the Maltz-Treves method.

Adolescent↗
PubMed1999

Simple scintigraphic parameters with Tc-99m galactosyl human serum albumin for clinical staging of chronic hepatocellular dysfunction.

Technetium-99m labeled diethylenetriaminepentaacetic acid (DTPA)-galactosyl human serum albumin (GSA) has been used for hepatocellular functional evaluation. This study proposed new and simple parameters to overcome the limitations of conventional parameters, and they were applied to the clinical staging of chronic liver dysfunction. The study group consisted of 93 patients including 81 with liver dysfunction and 12 control patients. In addition to the two conventional parameters, namely, receptor index (LHL15 = liver count divided by the sum of liver and heart counts at 15 minutes) and clearance index (HH15 = heart count at 15 minutes divided by the heart count at 3 minutes), 6 new parameters for Tc-99m GSA uptake and clearance were generated. The conventional receptor index of LHL15 showed a large variation depending on the size of region of interest (ROI) over the heart. The LHL15 normalized by the ROI size (nLHL15) showed more stable data and a better separation of mild liver dysfunction. A hyperbolic relationship between the LHL15 and HH 15 changed to a linear relationship by using the nLHL15 index. The combination of the liver to heart average count ratio at 15 minutes (LH 15) and T-half (minute) of the heart count also could differentiate each stage well. In conclusion, the use of the ROI-area normalized nLHL is recommended instead of the conventional LHL15. The indices of LH15 and T-half could be alternatively used as practical parameters for clinical staging in liver function.

Adult↗
PubMed1989

Assessment of hepatic excretory function in chronic liver disease by hepatobiliary scintigraphy.

Hepatobiliary scintigraphy was performed in 23 normal subjects and 47 patients with chronic liver disease (chronic hepatitis; n = 27, liver cirrhosis; n = 20) to evaluate its availability as a test of liver function. After intravenous administration of Tc-99m N-pyridoxyl-5-methyl-tryptophan, the data were acquired for 60 min and the time-activity curves of ROIs (the heart and liver) were generated. In two compartment model simulation, the early blood clearance rate (kl), late blood clearance rate (km), hepatic uptake rate (ku) hepatic excretion rate (ke), and hepatic excretion T 1/2 were calculated. There was no significant difference in those four k values in normal and chronic hepatitis. However, in liver cirrhosis each of them, except km, was lower than in normal subjects. The kl value correlated closely with the indocyanine green plasma clearance test, whereas the ke and T 1/2 values were closely correlated with the level of serum bilirubins. Only hepatobiliary scintigraphy showed the excretory function of the liver quantitatively and the ke value was helpful in detecting hepatic excretory dysfunction early in chronic liver disease before serum bilirubins increased.

Adolescent↗