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PubMed1984

Prospective evaluation of renal allograft dysfunction with 99mtechnetium-diethylenetriaminepentaacetic acid renal scans.

A prospective, single-blinded study was done to determine the ability of serial 99mtechnetium-diethylenetriaminepentaacetic acid scans to diagnose renal allograft rejection. Among 28 transplant recipients 111 renal scans were obtained 1 day postoperatively and every 3 to 4 days thereafter for 3 weeks in all patients retaining an allograft. Computer-generated time-activity blood flow curves were analyzed semiquantitatively for the 1) interval between curve peaks of the allograft and iliac artery, 2) renal transit time and 3) renal washout of radionuclide. Excretory function was assessed by degree and interval to appearance of radionuclide in the calices and bladder. Deterioration of renal blood flow and excretion compared to the initial scan was considered rejection. Of 52 scans performed during clinical rejection 47 (90.4 per cent) were interpreted as showing rejection (sensitivity). Of 53 scans interpreted as showing rejection 47 (88.7 per cent) were positive for clinical rejection. The remaining 6 patients (initial false positive results) suffered clinical rejection within 24 to 72 hours. We conclude that 99mtechnetium-diethylenetriaminepentaacetic acid renal scans are useful in the differential diagnosis of renal allograft dysfunction.

Clinical Trials as Topic↗
PubMed2004

Validation of the conceptual anatomical model of the lung airway.

The conceptual anatomical model of the lung airway considers each lung volume divided into ten concentric shells. It specifies the volume of each airway generation in each shell, using Weibel morphometry. This study updates and validates the model and evaluates the errors obtained when using it to estimate inhaled aerosol deposition per generation from spatial imaging data. A comparison of different airway models describing the volume per generation, including data from CT images of a lung cast and a human subject, was performed. A revised version of the conceptual model was created, using the average volume per generation from these data. The new model was applied to derive the aerosol deposition per generation from 24 single photon emission computed tomography (SPECT) studies. Analysis errors were assessed by applying the same calculations but using airway models based on the minimum and maximum volumes per generation. The mean shell position of each generation in the average model was not significantly different from either CT model. However there were differences between the volumes per generation of the different models. The root mean square differences between bronchial airways deposition fraction (generations 2-8) obtained from the maximum and minimum models compared to the new average model was 0.66 percentage points (14%). For the conducting airways deposition fraction (generations 2-15) this was 1.66 percentage points (12%). The conceptual model is consistent with CT measurements of airway geometry. The errors resulting from using a generic airway model to interpret 3D radionuclide image data have been defined.

Humans↗
PubMed2002

Effect of the size of regions of interest on the estimation of differential renal function in children with congenital hydronephrosis.

The estimation of differential renal function from dynamic renography affects clinical decisions. The estimation requires the kidneys to be delineated with regions of interest. However, in the presence of unilateral hydronephrosis it is not unusual for the affected kidney to be enlarged so that the regions of interest required to delineate the normal and abnormal kidneys are themselves dissimilar in size. The question, which then arises is, will this difference in the sizes of the regions of interest affect the resultant estimation of differential renal function? Eighteen children aged 1 month to 7 years, with prenatal ultrasound diagnosis of unilateral hydronephrosis where the affected kidney was larger than the normal kidney, underwent a total of 57 diuretic renograms using 99mTc-mercaptoacetyltriglycine. The renographic data were retrieved from optical disc and re-analysed. Regions of interest were generated which enclosed each kidney plus a region of interest of equal size to the abnormal large kidney was placed over the normal kidney. The consensus report from the Scientific Committee of Radionuclides in Nephrology described the Rutland-Patlak plot and integral methods for the estimation of differential renal function from dynamic renography. These two methods were used to analyse renal curves with and without background subtraction. Evaluation of the results suggest that technical factors, including the size of the region of interest, may affect differential renal function, and may, in part, explain the reports of the super-normal kidney in the literature.

Child↗
PubMed1982

Radionuclide angiography of the popliteal arteries in occlusive vascular disease.

Before undertaking a femoro-popliteal bypass graft it is important to know whether the popliteal artery is patent to receive the distal end of the graft. Patency was assessed in 48 studies of 46 patients with peripheral vascular disease by radio-nuclide angiography. The procedure consists of imaging the popliteal arteries using a gamma camera after a bolus injection of 99mTc-sodium pertechnetate. The radio-nuclide angiograms were compared with the operative X-ray popliteal angiograms. Reliable information was obtained from the radio-nuclide images regarding the patency of the popliteal artery provided a femoral pulse was present. Quantitative data generated from the activity time curves were of no value in assessment of the patency of the popliteal arteries.

Arterial Occlusive Diseases↗
PubMed1999

Binding of EGF peptide and EGF receptor antibodies and its fragments in different tumor models.

Binding of epidermal growth factor (EGF) to the EGF receptor is known to trigger a number of biological responses in the target cells including EGF receptor phosphorylation and stimulation of DNA synthesis leading to cell proliferation. Agents that bind to the EGF receptors could have a significant role in the therapy of tumors that express increased numbers of receptors by blocking the stimulatory effect of EGF. Different monoclonal antibodies (MAbs) directed to the EGF receptor have been generated that inhibit EGF binding and do not induce activation of the receptor tyrosine kinase. When there is sufficient uptake these antibodies can be used for immunotherapy and, after labeling with an appropriate radionuclide, also for radioimmunotherapy. For evaluation of a ligand as a therapeutic agent, it is necessary to investigate its binding characteristics in tumor cells and experimental tumors in vivo. Because the effectiveness of the antitumor activity of the MAb is dependent upon the amount of receptors in the tissue and the penetration of the MAb into the tissue, the receptor density, biokinetics, and tumor distribution of the MAb or its fragments were evaluated in different tumor models. The results of the experimental studies with tumor cell spheroids and different xenotransplanted human tumors have shown that the uptake and distribution in the tumor tissue is dependent on the molecular weight of the ligand. The correlation between the uptake of the substances and the receptor density is an indication for a noninvasive scintigraphic characterization of human tumors using radiolabeled compounds with specific binding to the tumor receptor and for selection of an optimal therapeutic regimen or radionuclide targeting of the tumor.

Animals↗
PubMedDate not supplied

[Biological effects in natural populations of small rodents in radiation contaminated areas. The frequency of bone marrow polyploid cells of bank voles in different years following Chernobyl accident].

On the basis of the metaphase analysis results, the peculiarities of dynamics of the genome mutation frequency (polyploid cells) were studied in bone marrow of bank voles inhabiting the areas with different radiocontamination level due to the Chernobyl accident (8-1526 kBq/m2 for 137Cs) in 1986-1991. Unexpectedly high frequencies of polypoid cells exceeding the pre-accidental level by a factor of 10(1)-10(3) were recorded in all populations studied. Relationship between the frequency of the parameter studied and the concentration of radionuclides incorporated in animal carcasses was proved. A statistically significant rise in the frequency of genome mutations with the time was revealed up to 1991, i.e. approximately to 12th post-accidental animal generation.

Animals↗
PubMed1980

An ultrapure germanium detector array for quantitating three-dimensional distribution of a radionuclide: a study of phantoms.

A new stationary 200-element ultrapure germanium (HPGe) array has been tested for accuracy and sensitivity in quantitating the distributed concentration of single-gamma-emitting radionuclides in phantoms approximating the size of the human brain. The phantoms consisted of 42 blocks of 39.1 cm3 average volume. Fourteen different permutations were studied. The concentrations in the blocks varied from 0i to 4.64 muCi/cm3. This first-generation instrument makes it possible to reconstruct the distributed concentration with a mean relative error of 8.3% at 200,000 counts per sample (1,000 counts/detector), and has sensitivities of 6,200 and 12,000 cps, respectively, for 1 muCi/cm3 of Xe-133 and Tc-99. The reconstruction algorithm is based on the conjugate gradient method of solving the set of linear equations that account for geometric, attenuation, and scatter factors. The results have implications for measuring the distribution of the partition coefficients, blood flow, blood volume, and concentration of tracers emitting single gamma photons in 42 anatomic subvolumes (30 cm3 average) of the entire brain simultaneously.

Cadmium↗
PubMed2004

Radionuclide imaging in drug development.

Radioactive tracers have made an immense contribution to the understanding of human physiology and pathology. At the start of the 21st century nuclear imaging has emerged as the main metabolic imaging modality which is of growing importance in drug development and clinical pharmacology. Using techniques adapted from those undertaken in clinical radiopharmacy and nuclear medicine facilities drug molecules and carrier systems may be radiolabelled and their release, biodistribution and uptake may be visualized in human subjects. Imaging studies are capable of locating the uptake of specific receptors in the brain, the site of disintegration of a tablet in the GI tract, the penetration of a nebulized solution into the lung and the residence time of an eye drop on the cornea. The technology uses suitable gamma emitting radionuclides such as 99mTc, 111In, 123I and 153Sm, which may be imaged with a gamma camera or positron emitters such as 11C, 13N, 15O and 18F for positron emission tomography (PET). Positron emitters are more appropriate for the direct labeling of drug molecules rather than metals such a 99mTc or 111In. A particular asset of these techniques is that the in vivo distribution and kinetics of a radiolabelled pharmaceutical formulation may be quantified. In this way correlation between the observed pharmacological effects and the precise site of delivery may be made. A powerful feature of nuclear molecular imaging is the evaluation of drug delivery systems in patient groups for whom the treatment is intended. Such studies not only provide data on the nature and characteristics of a product, such as reliability and reproducibility, but can demonstrate proof of principle for the new generation of targeted therapeutics. Imaging data are increasingly being used in product registration dossiers for submission to Regulatory Authorities.

Animals↗
PubMed1986

Background correction in first-pass radionuclide angiography: comparison of several approaches.

This study was designed to test the comparative accuracy of several commonly used background correction techniques in first-pass radionuclide angiography (FPRNA). Thirty patients underwent FPRNA and single plane contrast angiography (CA) within 1 hr of each other. The left ventricular ejection fractions (LVEF) calculated from the different background subtraction approaches to FPRNA were compared to the CA LVEF. When applied to a representative cycle, a horseshoe-shaped background region of interest (BKROI) underestimated LVEF (p less than 0.005, r = 0.91, s.e.e. = 0.06) while a ring shaped BKROI adjusted at end-systole for aortic valve motion insignificantly overestimated LVEF (p = NS, r = 0.91, s.e.e. = 0.07). A lung background approach applied to a representative cycle gave the best correlation with CA (p = NS, r = 0.96, s.e.e. = 0.04). Without using a representative cycle, time-activity curves from a horseshoe-shaped BKROI and the LV ROI were created and the LV curve was normalized to the peak counts in the BKROI curve. LVEF calculated from the normalized curve correlated favorably with CA LVEF (p = NS, r = 0.91, s.e.e. = 0.08). The influence of some recently described improvements in representative cycle generation are also documented.

Aged↗
PubMed1995

Closed-line integral optimization edge detection algorithm and its application in equilibrium radionuclide angiocardiography.

UNLABELLED: Automatic evaluation of left ventricular (LV) function using equilibrium radionuclide angiocardiography requires an edge detection algorithm to correct and reproducibly delineate the left ventricle. Available algorithms, usually based on differentiation of a radial profile, generally suffer from low precision due to low signal-to-noise ratios and overlapping structures, for example, the left atrium. METHODS: An edge detection algorithm was developed based on the assumption that the LV border can be defined as the maximum, normalized, closed-line integral of a closed curve in a vector field derived by image differentiation. It is further assumed that the closed curve can be described by a Fourier expansion with a limited number of harmonics. Regions of interest (ROIs) generated by this algorithm were compared with ROIs generated by an algorithm based on a combination of thresholding and second-order derivatives. RESULTS: This algorithm delineates the left ventricle and gives results more closely related to ROIs generated manually than the algorithm combining thresholding and the second-order derivative. Our algorithm can also handle the problem of overlapping structures, as demonstrated in phantom simulations. CONCLUSION: The concept of a maximum, normalized closed-line integral will improve the delineation of the LV in an equilibrium radionuclide angiocardiography study. The problem of overlapping structures is overcome by this algorithm because it takes into consideration global edge information.

Algorithms↗
PubMed2002

Nuclear medicine applications in molecular imaging.

With the emergence of the new field of molecular imaging, there is an increasing demand for development of sensitive and safe novel imaging agents that can be rapidly translated from small animal models into patients. Nuclear medicine and positron emission tomography (PET) techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes, usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at doses free of pharmacologic side effects, unlike the current generation of intravenous agents required for magnetic resonance (MR) and computed tomography (CT) scanning. In this article, we will review a representative sampling of the wide array of radiopharmaceuticals developed specifically for nuclear medicine radionuclide imaging that have been approved for clinical use, and those in pre-clinical trials. We will also review the existing strategies used to select the appropriate biologic markers and targets for radionuclide labeling that have been employed in the development of novel radiotracers and the imaging of small animals with new microSPECT (single photon emission computed tomography) technologies.

Animals↗
PubMed2002

Estimates of doses from global fallout.

This paper summarizes information about external and internal doses resulting from global fallout and presents preliminary estimates of doses resulting from intermediate fallout in the contiguous United States. Most of the data on global fallout were extracted from the reports of the United Nations Scientific Committee on the Effects of Atomic Radiation, in which the radiation exposures from fallout have been extensively reviewed at regular intervals. United Nations Scientific Committee on the Effects of Atomic Radiation estimated the average effective doses received by the world's population before 2000 to be about 0.4 mSv from external irradiation and 0.6 mSv from internal irradiation, the main radionuclide contributing to the effective dose being 137Cs. Effective doses received beyond 2000 result mainly from the environmentally mobile, long-lived 14C and amount to about 2.5 mSv summed over present and future generations. Specific information about the doses from fallout received by the United States population is based on the preliminary results of a study requested by the U.S. Congress and conducted jointly by the Centers for Disease Control and Prevention and the National Cancer Institute. Separate calculations were made for the tests conducted at the Nevada Test Site and for the high-yield tests conducted mainly by the United States and the former Soviet Union at sites far away from the contiguous United States (global tests). The estimated average doses from external irradiation received by the United States population were about 0.5 mGy for Nevada Test Site fallout and about 0.7 mGy for global fallout. These values vary little from one organ or tissue of the body to another. In contrast, the average doses from internal irradiation vary markedly from one organ or tissue to another; estimated average thyroid doses to children born in 1951 were about 30 mGy from Nevada Test Site fallout and about 2 mGy from global fallout.

Nevada↗
PubMed1985

Effects of pleural pressure and abdominal pressure on diaphragmatic blood flow.

The aim of this experiment was to determine if blood flow to the diaphragm is affected by generating the transdiaphragmatic pressure mainly with positive abdominal pressure or mainly with negative pleural pressure, during both sustained and intermittent diaphragmatic contractions. Diaphragmatic blood flow was measured in anesthetized mongrel dogs by the radionuclide-labeled microsphere method. Sustained and intermittent tetanic diaphragmatic contractions were produced with 1) free abdomen and closed chest (high negative pleural pressure) and 2) bound abdomen and open chest (high positive abdominal pressure). During sustained contractions, diaphragmatic blood flow at maximum levels of activation was significantly higher with negative pleural pressure (P less than 0.05). In contrast with this, intermittent diaphragmatic contractions did not yield a significant difference between diaphragmatic blood flow with negative pleural pressure and with positive abdominal pressure at maximal levels of transdiaphragmatic pressure. During both sustained and intermittent contractions, blood pressure, as measured from the carotid artery, did not vary significantly between negative pleural pressure and positive abdominal pressure. We conclude that during sustained tetanic diaphragmatic contractions, diaphragmatic blood flow is obstructed by high positive abdominal pressures, but during intermittent diaphragmatic contractions, high positive abdominal pressures do not affect total blood flow, since any inhibition of blood flow during the contractile period can be compensated for during the relaxation period between contractions.

Abdomen↗
PubMed1989

[Detection of coronary artery disease by exercise radionuclide ventriculography: using sector analysis].

Exercise first-pass radionuclide ventriculography was performed on 65 patients with coronary artery disease (CAD) and 18 control subjects with normal coronary artery, Left ventricle (LV) was divided into 5 sectors in radial, and volume curves were generated for whole LV and each sector for estimating LVEF and time to end systole (TES). The differences of TES between whole LV and each sector were calculated and these 5 differences were averaged (Variation of TES). We defined this Variation of TES as an index of LV asynchrony, and used for detection of CAD. The overall sensitivity and specificity for identifying CAD were 63% and 83% (LVEF during exercise), 51% and 83% (delta LVEF). Variation of TES during exercise had a sensitivity and a specificity of 88% and 83%, and was more sensitive than both LVEF during exercise and delta LVEF (p less than 0.01). In conclusion, Variation of TES was a good marker of LV asynchrony and useful for the detection of CAD.

Coronary Disease↗
PubMed1996

Accurate measurement of copper-67 in the presence of copper-64 contaminant using a dose calibrator.

UNLABELLED: The use of 67Cu-labeled antibodies for the treatment of cancer has advanced to the clinical trial phase. Quantitation of 67Cu radiopharmaceuticals is complicated by the presence of the radioimpurity of 64Cu in 67Cu supplies. Here we report a method to assay 67Cu and 64Cu in a mixed sample with a commonly available instrument, the ionization chamber dose calibrator. METHODS: The activities of 67Cu and 64Cu in a mixed sample can be calculated from a single-dose calibrator measurement. The calculation requires (1) instrument-specific response coefficients D67 and D64, generated by gauging the instrument for the efficiency of measurement of 67Cu and 64Cu, and (2) a value for the ratio of 67Cu to 64Cu in the sample, routinely provided by major suppliers of 67Cu. D67 and D64 were empirically determined by measuring samples containing known amounts of 67Cu and 64Cu. The samples were also assayed by gamma ray spectroscopy to verify the isotope ratios given by the suppliers. RESULTS: This method generated accurate response coefficients. At the recommended dose calibrator setting for the measurement of 67Cu, at which D67 = 1.0, the measurement for D67 with this method was 1.02 (+/- 0.04). Isotope ratios provided by the radionuclide suppliers were corroborated by gamma ray spectroscopy. CONCLUSION: A method is presented by which 67Cu and 64Cu in a mixed sample can be assayed using a dose calibrator. Although the derived numeric constants are only correct for a specific dose calibrator and setting, the method can be adapted for use with any dose calibrator.

Calibration↗
PubMed1985

Computer-assisted radionuclide perfusion study in solitary cold thyroid nodules for diagnosis of malignancy.

A computer-assisted radionuclide perfusion study was performed in 25 cases of solitary 'cold' thyroid nodules to assess their vascularity relative to that of normal adjoining thyroid tissue. Hypervascularity was seen in 3 malignant nodules; 1 follicular adenoma also showed increased vascularity. The 21 nodules demonstrating equal vascularity or avascularity with respect to normal thyroid tissue were benign in nature. Computer-generated time-activity curves were helpful in distinguishing hypervascular from equally vascular nodules. This technique, in conjunction with clinical evaluation, can be of value in deciding whether patients should undergo surgery or receive conservative management.

Adult↗
PubMed1990

The chemistry of 99mTc-labeled radiopharmaceuticals.

The subject of the chemistry of 99mTc-radiopharmaceuticals consists of a collection of bits and pieces of information without a unifying theme. Since the initial impetus to the field of organ imaging was provided by radiochemists, nuclear chemists, and clinician-investigators, using easily prepared 99mTc-compounds from available off-the-shelf ligands, complete chemical characterization was not carried for the 99mTc-radiopharmaceuticals and their metabolites. The influx of coordination, organic, and analytic chemists and their systematic studies clarified some of the structures of these tracers, and promoted the general synthetic methods of a variety of ligands and the corresponding 99mTc-chelates as well as understanding of the nature of their metabolites. Although major developments for organ-imaging radiopharmaceuticals had been made, future studies will result in the simplified methodology of protein-labeling, fine-tuning of the currently available radiopharmaceuticals for higher organ-extraction, and replacement of expensive 123I-labeled tracers with the corresponding 99mTc-tracers. In general, the Tc-complexes are thermodynamically less stable and kinetically more labile than the corresponding Re-complexes. The well established chemistry of Re-compounds, the similarity of Tc-chemistry to that of Re compounds, and structure-activity relationships of a few classes of 99mTc-labeled compounds, may promote the development of new generation of 99mTc-labeled radiopharmaceuticals.

Animals↗
PubMed1982

First-pass radionuclide angiocardiography in the determination of left-to-right cardiac shunt site in children.

To ascertain if the level of a left-to-right cardiac shunt can be reliably established by first-pass radionuclide angiocardiography with 99mTc-pertechnetate, 102 children have been studied; 19 without a shunt, 26 with an atrial septal defect (ASD), 45 with a ventricular septal defect (VSD), and 12 with a patent ductus arteriosus (PDA). Time-activity curves were generated over the right atrium and ventricle, and several quantitative parameters were derived from the curves. It was concluded that in the absence of right-sided valvular incompetence, the time-activity curves show the greatest abnormality in the cardiac chambers distal to the left-to-right shunt. The right ventricular curve is typically altered in ASD but cannot be relied upon to differentiate VSD or PDA. The identification of ASD is assisted by the use of two of the parameters, the count ratio C4:C1 and time ratio T2-T1.

Adolescent↗