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A new approach to image subtraction in immunoscintigraphy: preliminary results.

Recently proposed image comparison software is applied to immunoscintigraphy. The software performs geometric and gray level registration of two images and generates an image of the statistically significant differences. It permits the comparison of scintigraphic images recorded at different times. It is used to subtract 113mIn and 111Inphytate colloid liver scans and early (blood pool) images from 131I or 111In-monoclonal Ab images and to compare Ab images recorded at different times. Using the procedures made possible by this software, only images recorded using the same radionuclide or using radionuclides of about the same energy are compared. Anti CEA, 19-9 and OC 125 F(ab)2 fragments labeled with 131I or 111In are used in 32 patients with 47 demonstrated recurrences or metastases of colorectal or ovarian cancers. The overall sensitivities of the unprocessed and processed images are 25/47 and 41/47 respectively. The improvement in sensitivity is particularly high in the liver when In labelled Ab are used. This technique improves the contrast of the images, but the interpretation must take into account the components of the non target activity (kidney, bone marrow, colon...) which are not removed by the image subtraction method.

Antibodies, Monoclonal↗

Characterization of the TE-NORM waste associated with oil and natural gas production in Abu Rudeis, Egypt.

The present study was conducted to characterize the Technically Enhanced Naturally Occurring Radioactive Materials (TE-NORM) waste generated from oil and gas production. The waste was characterized by means of dry screening solid fractionation, X-ray analysis (XRF and XRD) and gamma-ray spectrometry. Sediment of the TE-NORM waste was fractionated into ten fractions with particle sizes varying from less than 100 microm to more than 3 mm. The results showed that the TE-NORM waste contains mainly radionuclides of the 238U, 235U and 232Th series. The mean activity concentrations of 226Ra (of U-series), 228Ra (of Th-series) and 40K in the waste samples before fractionation (i.e. 3 mm) were found to amount to 68.9, 24 and 1.3 Bq/g (dry weight), respectively. After dry fractionation, the activity concentrations were widely distributed and enriched in certain fractions. This represented a 1.48 and 1.82-fold enrichment of 226Ra and 228Ra, respectively, in fraction F8 (2.0-2.5 mm) over those in bulk TE-NORM waste samples. The activity ratios of 238U/226Ra, 210Pb/226Ra, 223Ra/226Ra and 228Ra/224Ra were calculated and evaluated. Activity of the most hazardous radionuclide 226Ra was found to be higher than the exemption levels established by IAEA [International Atomic Energy Agency, 1994. International Basic Safety Standards for the Protection against Ionizing Radiation and for the Safety of Radiation Sources. GOV/2715/94, Vienna]. The radium equivalent activity (Ra-eq), radon (222Rn) emanation coefficient (EC) and absorbed dose rate (Dgammar) were estimated and these are further discussed.

Egypt↗

Evolution of Tc-99m in diagnostic radiopharmaceuticals.

The progress in diagnostic nuclear medicine over the years since the discovery of 99mTc is indeed phenomenal. Over 80% of the radiopharmaceuticals currently being used make use of this short-lived, metastable radionuclide, which has reigned as the workhorse of diagnostic nuclear medicine. The preeminence of 99mTc is attributable to its optimal nuclear properties of a short half-life and a gamma photon emission of 140 keV, which is suitable for high-efficiency detection and which results in low radiation exposure to the patient. 99mTcO4-, which is readily available as a column eluate from a 99Mo/99mTc generator, is reduced in the presence of chelating agents. The versatile chemistry of technetium emerging from the 8 possible oxidation states, along with a proper understanding of the structure-biologic activity relationship, has been exploited to yield a plethora of products meant for morphologic and functional imaging of different organs. This article reviews the evolution of 99mTc dating back to its discovery, the development of 99Mo/99mTc generators, and the efforts to exploit the diverse chemistry of the element to explore a spectrum of compounds for diagnostic imaging, planar, and single photon emission computed tomography. A brief outline of the 99mTc radiopharmaceuticals currently being used has been categorically presented according to the organs being imaged. Newer methods of labeling involving bifunctional chelating agents (which encompass the "3 + 1" ligand system, Tc(CO)3(+1)-containing chelates, hydrazinonicotinamide, water-soluble phosphines, and other Tc-carrying moieties) have added a new dimension for the preparation of novel technetium compounds. These developments in technetium chemistry have opened new avenues in the field of diagnostic imaging. These include fundamental aspects in the design and development of target-specific agents, including antibodies, peptides, steroids, and other small molecules that have specific receptor affinity.

Bone and Bones↗

Detection and quantification of regional wall motion abnormalities using phase analysis of equilibrium gated cardiac studies.

Phase images obtained from equilibrium gated cardiac studies were evaluated for qualitative and quantitative information and correlated with contrast angiography in 33 patients. The left ventricular region of interest was obtained by a semiautomatic procedure which avoided underestimation of size but also eliminated extraventricular pixels. Phase images and phase distribution histograms were arranged in three standard displays which included the whole heart, isolated left ventricle, isolated abnormal areas, and quantification of maximum phase shift in the whole free border and in the inferolateral and posterolateral segments. Only the free left ventricular border was evaluated. According to contrast angiography results, four categories were obtained: normal, hypokinetic, akinetic, and dyskinetic. The best correlation with contrast angiography was found with the results obtained by dividing the left ventricular free border in two segments (r = 0.91). Scheffe's test for multiple comparisons showed significant differences between each of the four categories. Expressed in phase shifts from the histogram mode, the lower limits for the three abnormal categories were established at 30 degrees, 78 degrees, and 156 degrees respectively for hypokinetic, akinetic, and dyskinetic segments. For distinguishing normal from abnormal segments, sensitivity = 83%, specificity = 94%, and accuracy = 89%. The main reasons for discrepant results appeared to be small hypokinetic areas in an otherwise normal ventricle, very large area of hypokinesia, segments adjacent to an area of marked abnormality, and ventricles with asynchrony (wave-like motion). The method described provides an image which characterizes myocardial synchrony, generates clear boundaries for abnormal areas, and lends itself to quantification.

Adolescent↗

Time profile; space- and time-condensed images.

A method has been developed to generate "condensed images" and to produce instantaneously time-activity curves from rectangular regions of interest. It uses readily available tomographic software. Examples of esophageal transit and thyroid perfusion are shown. Further developments are discussed.

Esophagus↗

Alterations in immunoglobulin synthesis by peripheral blood mononuclear cells from splenectomized patients with and without splenic regrowth.

Unstimulated and pokeweed mitogen (PWM)-stimulated immunoglobulin (Ig) synthesis by peripheral blood mononuclear cells (PBMC) in vitro, serum Ig concentrations, and the degree of splenic regrowth was studied in 33 patients who had been splenectomized following trauma. The concentration of IgG and IgA was significantly raised in the supernatants of unstimulated cultures of PBMC from the patients. The stimulation of Ig synthesis by PWM, measured as a stimulation index (SI), was significantly less in the culture of PBMC from the patients, compared with the controls. The SI was reduced both in those patients whose unstimulated PBMC secreted normal concentrations of IgG and IgA in culture, as well as in those whose cells secreted elevated concentrations of Ig. The concentration of IgM in the serum of the patients was significantly reduced compared with the controls, the serum IgG was raised, and the serum IgA was not altered. The degree of splenic regrowth (splenosis) was measured in the patients by splenic scanning, by using heat-damaged, radiolabeled autologous erythrocytes. The patients were allocated into four groups, depending on whether they had no (11 patients), minimal (11), moderate (seven), or large (four) splenosis. There was no difference between any of the groups with respect to the synthesis of IgG or IgA in culture or the serum Ig concentrations. These results indicate that Ig synthesis by PBMC in vitro, and serum Ig concentrations in vivo, are abnormal in patients who have been splenectomized for trauma, and that the generation of splenosis tissue does not correct these changes.

Adolescent↗

Improved radionuclide method for assessment of pulmonary artery pressure in COPD.

An improved method of noninvasive assessment of pulmonary arterial pressure is presented. The already existing radionuclide method for assessment of pulmonary arterial pressure based on right ventricular ejection fraction, although having a relatively good positive predictive accuracy (75 percent), lacks in specificity and correlates only weakly with pulmonary arterial pressure, r = .66. In the present study a diastolic index of the ventricular performance (right atrial early diastolic emptying rate) was used to improve the predictive value of the right ventricular ejection fraction. Phase image analysis was used to differentiate the right atrium from the rest of the cardiac structures, and right atrial emptying rate was calculated after time activity curves were generated. A reasonably good correlation was found between right atrial emptying rate and pulmonary arterial pressure, r = .75. This diastolic index, however, was limited in its ability to detect patients with COPD and normal pulmonary arterial pressure (negative predictive value 62 percent). In order to improve the predictive value of right ventricular ejection fraction, having low specificity (33 percent) but high sensitivity (93 percent), a score index was constructed, combining right ventricular ejection fraction with right atrial emptying rate (having high specificity 100 percent, but modest sensitivity 78 percent). Score index proved to be an excellent indicator of pulmonary arterial hypertension (positive predictive value 93 percent, negative predictive value 100 percent.

Adult↗

Radionuclide left ventricular ejection fraction: a comparison of three methods.

Three commercially available computer programs (a semiautomatic method, a manual method, and a regional method) were used to calculate left ventricular ejection fraction from the equilibrium multiple gated radionuclide ventriculograms obtained from 24 normal male subjects and 20 men with heart failure. In the normal subjects the ejection fraction values calculated by each method were significantly different (mean SD) difference between semiautomatic and manual 3.3 (5.8); between semiautomatic and regional 12.0 (6.3); and between manual and regional 8.7 (6.9]. In the patients with heart failure the ejection fraction values calculated by the semiautomatic method differed significantly from those calculated by the manual and regional methods (mean (SD) difference between semiautomatic and manual 3.4 (4.7); between semiautomatic and regional 4.9 (4.9); and between manual and regional 1.5 (6.2]. The ejection fraction values obtained by the semiautomatic method were generally higher and more consistent than those derived from the manual and regional methods. An ejection fraction of greater than or equal to 50% with the semiautomatic method would be regarded as normal but if the same normal range was applied to the regional method nine (38%) of the 24 normal subjects would appear to have an abnormal left ventricular function. Clinicians should be aware that the method used to generate a time-activity curve is an important consideration in the calculation of ejection fraction. Each centre should establish its own range and reproducibility for the method it uses to measure ejection fraction. These values should not be assumed to apply to any other method.

Adult↗

Risk estimates for deterministic health effects of inhaled weapons grade plutonium.

Risk estimates for deterministic effects of inhaled weapons-grade plutonium (WG Pu) are needed to evaluate potential serious harm to (1) U.S. Department of Energy nuclear workers from accidental or other work-place releases of WG Pu; and (2) the public from terrorist actions resulting in the release of WG Pu to the environment. Deterministic health effects (the most serious radiobiological consequences to humans) can arise when large amounts of WG Pu are taken into the body. Inhalation is considered the most likely route of intake during work-place accidents or during a nuclear terrorism incident releasing WG Pu to the environment. Our current knowledge about radiation-related harm is insufficient for generating precise estimates of risk for a given WG Pu exposure scenario. This relates largely to uncertainties associated with currently available risk and dosimetry models. Thus, rather than generating point estimates of risk, distributions that account for variability/uncertainty are needed to properly characterize potential harm to humans from a given WG Pu exposure scenario. In this manuscript, we generate and summarize risk distributions for deterministic radiation effects in the lungs of nuclear workers from inhaled WG Pu particles (standard isotopic mix). These distributions were developed using NUREG/CR-4214 risk models and time-dependent, dose conversion factor data based on Publication 30 of the International Commission on Radiological Protection. Dose conversion factors based on ICRP Publication 30 are more relevant to deterministic effects than are the dose conversion factors based on ICRP Publication 66, which relate to targets for stochastic effects. Risk distributions that account for NUREG/CR-4214 parameter and model uncertainties were generated using the Monte Carlo method. Risks were evaluated for both lethality (from radiation pneumonitis) and morbidity (due to radiation-induced respiratory dysfunction) and were found to depend strongly on absorbed-dose-rate history (which depends on WG Pu solubility). The results obtained were compared to new data from animal and epidemiological studies. Our findings suggest that NUREG/CR-4214 models for assessing lethality risk from inhaled radionuclides may need some modest revision in light the new data. However, for assessing morbidity risks, major revisions may be needed.

Administration, Inhalation↗

Radiolabeled anti-lymphoma antibodies.

This promises to be an era of remarkable change for patients afflicted with NHL. Although the cause of NHL remains unknown, there is greater understanding of 'these diseases' at the molecular level. Insights into genetic aberrations that interrupt apoptosis or that promote proliferation have profound implications for the future management of NHL (and other malignancies). Ongoing trials of immunotherapy and RIT continue to show excellent response rates in patients with relapsed or refractory NHL and remarkably favorable safety and toxicity profiles. More drug approvals can be anticipated. As antibody engineering progresses, formerly theoretical questions regarding optimized targeting and antibody affinity, take on relevance and practicality [65]. The ability to generate new constructs, such as bivalent antibodies, or fusion proteins incorporating two disparate functional proteins, presents exciting opportunities for radiopharmaceutical development. The role of bifunctional antibodies in tumor targeting is likely to increase in importance, both as a means of targeting, and as a technique for increasing MAb specificity [66,67]. Pretargeting approaches are in development as a way of decreasing the amount of time that the radionuclide circulates in the blood (radiating normal tissues) thereby allowing the administration of higher doses of radionuclide (radioactivity and radiation) [67-69].

Animals↗

Experimental approaches to myocardial function studies: C15 O2 and 81m Kr.

The role of short-lived gaseous radiotracers in myocardial function studies is reviewed. The evaluation of shunts and ejection fractions characterizing individual chambers is best performed with tracers restricted to those chambers. Classic examples include the C15 O2 inhalation radiocardiogram for probing the left-heart performance, with the right heart illuminated by intravenous 133Xe in saline. A more elegant utilization of rapid physical decay to unravel flow patterns is seen in the use of 81m Kr. Krypton-81m is swept from its parent 81Rb, either confined to an extracorporeal generator or an in vivo rubidium distribution. The steady-state images that result contain a wealth of dynamic information distilled into its most lucid format.

Carbon Dioxide↗

Protection of plasmid DNA by a Ginkgo biloba extract from the effects of stannous chloride and the action on the labeling of blood elements with technetium-99m.

Ginkgo biloba extract (EGb) is a phytotherapeutic agent used for the treatment of ischemic and neurological disorders. Because the action of this important extract is not fully known, assays using different biological systems need to be performed. Red blood cells (RBC) are labeled with technetium-99m (Tc-99m) and used in nuclear medicine. The labeling depends on a reducing agent, usually stannous chloride (SnCl2). We assessed the effect of different concentrations of EGb on the labeling of blood constituents with Tc-99m, as sodium pertechnetate (3.7 MBq), and on the mobility of a plasmid DNA treated with SnCl2 (1.2 microg/ml) at room temperature. Blood was incubated with EGb before the addition of SnCl2 and Tc-99m. Plasma (P) and RBC were separated and precipitated with trichloroacetic acid, and soluble (SF-P and SF-RBC) and insoluble (IF-P and IF-RBC) fractions were isolated. The plasmid was incubated with Egb, SnCl2 or EGb plus SnCl2 and agarose gel electrophoresis was performed. The gel was stained with ethidium bromide and the DNA bands were visualized by fluorescence in an ultraviolet transilluminator system. EGb decreased the labeling of RBC, IF-P and IF-RBC. The supercoiled form of the plasmid was modified by treatment with SnCl2 and protected by 40 mg/ml EGb. The effect of EGb on the tested systems may be due to its chelating action with the stannous ions and/or pertechnetate or to the capability to generate reactive oxygen species that could oxidize the stannous ion.

Animals↗

The effect of source size on the buildup factor calculation of absolute volume.

A general scheme for generating attenuation-corrected images for use in absolute volume measurements has been developed. The technique is based on a buildup factor approach for Compton scatter compensation and requires anterior and posterior count-rate measurements. The scatter correction requires evaluation of the attenuation factor (1-(1-e-mu d)B(infinity), where mu is the linear attenuation coefficient in cm-1 and B(infinity) is the buildup factor at infinite depth. The attenuation factors for four different source sizes using 99mTcO4- and a 20% scintillation camera energy window are reported. The results indicated that B(infinity) was constant while mu varied as a function of size (S) in pixels according to mu = 0.151 cm-1 X exp(-1.18 X 10(-4) pixels-1 X S). Once the appropriate value of mu was determined, a pair of anterior-posterior count rate equations was used to generate attenuation-corrected count rate data for use in absolute volume measurements. The method was validated by calculating three separate phantom volumes. The results showed that the method provides less than +/- 6.0% error for volume determinations at all investigated depths.

Mathematics↗

Comparison of theoretical and experimental particle diffusion data within human airway casts.

The dose delivered to airway cells is a critical factor whether one is addressing the therapeutic (i.e., positive) effects of inhaled pharmacologic agents or the toxic (i.e., negative) effects of pollutants. In this study, theoretical models describing particle deposition have been compared with experimental data from the literature. In the simulations, airways can be either rough-or smooth-walled to be consistent with human lungs which can be either lined by cartilaginous rings (i.e., rough) or muscle (i.e., smooth). Particle motion for rough-walled airways within generations I = 1-6 is calculated using the formula proposed by Martonen et al. (1). For smooth-walled airways within generations I = 7-10, particle motion is calculated using the formula proposed by Martonen et al. (2). Theoretical predictions of particle deposition efficiencies are not only in agreement with the overall best fit empirical correlation presented by Cohen and Asgharian (3) over a wide range of dimensionless diffusion parameters, but also match individual experimental measurements (only available in I = 1-6) with regard to effects of the parameters of particle size, flow rate, and airway dimensions. The mean difference in the ratio of experimental-to-theoretical particle diffusion values is 0.9 for a flow rate of 18 L/min and 1.1 for a flow rate of 34 L/min (i.e., the difference is only about 10%) within the upper airways of the casts (airway generations I = 1-6), the mean difference for the whole casts was much greater. This may be attributed to the uncertainty of flow conditions in the peripheral airways as a result of the trimmed nature of the casts. Overall, the findings suggest that the model can be a valuable component of aerosol therapy and risk assessment protocols, especially to address effects of enhanced deposition of pharmacologic drugs and radionuclides at sites within the human tracheobronchial tree.

Administration, Inhalation↗

Advancements in cancer therapy with alpha-emitters: a review.

PURPOSE: This synopsis attempts to shed light on the progresses made in the field of cancer therapy using alpha-particles. HURDLES AND PROGRESSES: The rationale of selection of radionuclides focusing on comparison of alpha- and beta-emitters, the hurdles and their solutions, and recent developments are addressed. The efforts made in the field of alpha-radioimmunotherapy of hematologic malignancies are emphasized. A good deal of progress has been achieved in the past decade, and preclinical studies with a variety of radioimmunoconjugates with astatine and bismuth radioisotopes (At-211, Bi-212, and Bi-213) have generated encouraging results, providing an impetus for future clinical trials. CONCLUSION: The onset of early clinical trials with alpha-emitters will hopefully enable the cancer researchers to come up with extremely effective and highly specific "smart bombs" to target cancer cells.

Actinium↗

A correlative study between 99mTc-ESTCPTA and 99mTc-MIBI in rats.

Tissue distribution of the 99mTc labeled derivative of the estrogen compound 3,17-alpha-estradiolyl propyl 1,4,8,11-tetraazacyclotetradecanyl-l-(4-methylbenzoic acid) ester (ESTCPTA), which has an 3,17-alpha-estradiolyl propinol coupled to l-(4-methylbenzoic acid)1,4,8,11-tetraazacyclotetradecane (CPTA), was compared to 99mTc-MIBI (methoxyisobutyl isonitrile) in female Albino Wistar rats. Tissues of interest included lung, liver, heart, kidneys, spleen, stomach, intestines, pancreas, muscle, blood, breast, ovary, fat, and uterus. 99mTc-ESTCPTA uptake by the uterus and ovary, as ER-rich tissues, was highly selective. Maximum uptakes for 99mTc-MIBI and 99mTc-ESTCPTA are 90 min in breast, ovary and uterus. The pancreas also showed significant receptor saturated and unsaturated ratios for 99mTc-ESTCPTA. Results are sufficiently encouraging to generate further evaluation of these and related compounds as possible estrogen receptor based tumor imaging and therapeutic agents in estrogen-rich tissues.

Animals↗

Practical aspects of indirect lymphography and lymphoscintigraphy.

The objective of this presentation is to discuss practical issues related to the use of indirect lymphography and lymphoscintigraphy in the differential diagnosis of lymphedema. Indirect lymphography demonstrates the filling of initial lymphatics and of lymph collectors. Lymphoscintigraphy is utilized to generate morphological and functional imaging information about the lymphatic drainage. For the functional evaluation of lymphatic drainage, quantitative measurement of the lymph node uptake can be performed. The practical implications of these diagnostic interventions are discussed.

Edema↗

Simultaneous reconstruction, segmentation, and edge enhancement of relatively piecewise continuous images with intensity-level information.

A multinomial image model is proposed which uses intensity-level information for reconstruction of contiguous image regions. The intensity-level information assumes that image intensities are relatively constant within contiguous regions over the image-pixel array and that intensity levels of these regions are determined either empirically or theoretically by information criteria. These conditions may be valid, for example, for cardiac blood-pool imaging, where the intensity levels (or radionuclide activities) of myocardium, blood-pool, and background regions are distinct and the activities within each region of muscle, blood, or background are relatively uniform. To test the model, a mathematical phantom over a 64 x 64 array was constructed. The phantom had three contiguous regions. Each region had a different intensity level. Measurements from the phantom were simulated using an emission-tomography geometry. Fifty projections were generated over 180 degrees, with 64 equally spaced parallel rays per projection. Projection data were randomized to contain Poisson noise. Image reconstructions were performed using an iterative maximum a posteriori probability procedure. The contiguous regions corresponding to the three intensity levels were automatically segmented. Simultaneously, the edges of the regions were sharpened. Noise in the reconstructed images was significantly suppressed. Convergence of the iterative procedure to the phantom was observed. Compared with maximum likelihood and filtered-backprojection approaches, the results obtained using the maximum a posteriori probability with the intensity-level information demonstrated qualitative and quantitative improvement in localizing the regions of varying intensities.

Algorithms↗