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PubMed1990

Gynecologic tumor markers.

The advent of monoclonal technology has increased the potential utility of antibody-dependent tumor marker assays in gynecologic oncology. The availability of unlimited quantities of several pure monoclonal antibodies directed against novel epitopes on tumor-associated antigens has permitted development of highly sensitive assays for serum markers. Traditional assays for human chorionic gonadotropin (hCG), NB/70K and TA-4 have been improved. CA 125 has provided a useful first-generation marker for monitoring ovarian cancer and triaging patients with pelvic masses, despite limitations in sensitivity and specificity. In the next decade, the challenge is to identify new markers that will complement CA 125 in monitoring ovarian cancer and facilitate screening for occult early-stage disease. Strategies involving multiple markers and modalities may be required. Some markers may emerge through a more fundamental knowledge of the biology of gynecologic neoplasms, including the expression of growth factors and their receptors. Finally, the application of monoclonal antibodies to immunohistochemistry and radionuclide imaging also may provide new areas of diagnostic application for monoclonal antibodies in gynecologic oncology.

Antibodies, Monoclonal↗
PubMed2005

Natural radioactivity in Brazilian groundwater.

More than 220 groundwater samples were analyzed for 228Ra, 226Ra, 222Rn, 210Pb, U(nat), Th(nat), pH, conductivity, fluoride and some additional elements determined by ICP-MS. Since samples from several Brazilian states were taken, involving areas with quite different geologies, no general trend was observed relating the chemical composition and the natural radionuclide content. On the other hand, 210Pb strongly depends on the water content of its progenitor, 222Rn. The values obtained during the present work were compared with those reported by Hainberger et al. [Hainberger, P.L., de Oliveira Paiva, I.R., Salles Andrade, H.A., Zundel, G., Cullen, T.L., 1974. Radioactivity in Brazilian mineral waters. Radiation Data and Reports, 483-488.], when more than 270 groundwater samples were analyzed, mainly, for 226Ra. Based on the results of both works, it was possible to build a database including the results of both works, generating a set with the radium content of circa 350 groundwater sources. It was demonstrated that 228Ra, 226Ra, 222Rn, 210Pb and U(nat) content in Brazilian groundwater follows a lognormal distribution and the obtained geometric mean were 0.045, 0.014, 57.7, 0.040 BqL(-1) and 1.2 microgL(-1), respectively.

Brazil↗
PubMed1989

Future role of radiolabeled monoclonal antibodies in oncological diagnosis and therapy.

This review discusses the current limitations and future prospects of radiolabeled antibodies in cancer imaging (radioimmunodetection, or RAID) and therapy (radioimmunotherapy, or RAIT). Aspects such as the antibody vehicle, antigen target, radiolabel, tumor, host, and RAID and RAIT procedures are considered. In the short timespan for the development of RAID, tumors as small as 0.5 cm, which are sometimes missed by other radiological methods, can now be imaged with antibody fragments labeled with suitable radionuclides (eg, 111In, 123I, and 99mTc), particularly when single photon emmission computed tomography (SPECT) scanning methods are employed. 99mTc is clearly the preferred label, and the recent development of simple and rapid methods to attach this isotope to antibodies should be a welcome advance for the more widespread use of RAID. In RAIT, radiosensitive neoplasms, such as lymphomas, are already showing impressive responses to 131I-labeled antilymphoma murine monoclonal antibodies. Therefore, the successful conjugation of beta- and alpha-emitters to "humanized" monoclonal antibodies should provide a new generation of promising cancer therapeutics.

Antibodies, Monoclonal↗
PubMed1982

Detection of lesions in thallium-201 myocardial perfusion scintigraphy.

Experimental studies have been made of the lesion detectability in myocardial perfusion studies using thallium-201. A series of images (AP-view) was generated using a convolution of a mathematical model of the left ventricular myocardium and an experimentally determined point spread function. Background was added. Images were simulated with 100 k, 200 k, and 300 k counts for the complete image. Each image contained a lesion with either 0% or 50% of the normal tracer concentration. All images were interpreted by five experienced observers, independently of each other. Their interpretations were analysed using the Kolmogorov-Smirnov two sample test. The true positive fraction (TPF) was hardly affected by changes in count density. The TPF decreased significantly if the lesion tracer concentration changed from 0% to 50% of the normal myocardial tracer concentration. The decrease was independent of the count density. The false positive fraction (FPF) decreased significantly if the count density increased; no difference in FPF was found for a change in lesion tracer concentration. In addition, plots were generated with the TPF versus lesion volume. The TPF was lowest for locations far from the camera; FPF was high for these segments. Increase of the count density mainly improved the FPF in these segments. Small lesion were more difficult to detect.

Heart Diseases↗
PubMed1990

A comparison of 131I-labeled antibodies, 2-deoxy-2-[18F]fluoro-D-glucose and 68Ga-EDTA in the imaging of human tumor xenografts in nude mice.

Three different biological properties--glucose metabolism, gallium imaging and antigen-antibody interaction--have been targeted to image human tumor xenografts implanted in nude mice. Seventy-two experiments were performed in 25 nude mice. Two types of human tumors were used: colorectal carcinoma SW 1116 and melanoma WM 9. Immunoscintigraphic studies produced the highest tumor sampling and confirmed earlier findings that F(ab')2 fragments generate better tumor images than whole antibodies.

Animals↗
PubMed2000

Targeting aerosol deposition in patients with cystic fibrosis: effects of alterations in particle size and inspiratory flow rate.

STUDY OBJECTIVE: To determine if aerosolized medications can be targeted to deposit in the smaller, peripheral airways or the larger, central airways of adult cystic fibrosis (CF) patients by varying particle size and inspiratory flow rate. DESIGN: Randomized clinical trial. SETTING: Outpatient research laboratory. PATIENTS: Nine adult patients with CF. INTERVENTIONS: Patients inhaled an aerosol comprised of 3.68+/-0.04 microm saline solution droplets (two visits) or 1.01+/- 0.2 microm saline solution droplets (two visits) for 30 s, starting from functional residual capacity and breathing at a slow or faster inspiratory flow rate. On all visits, the saline solution was admixed with the radioisotope (99m)Tc. Immediately after inhalation, a gamma camera recorded the deposition pattern of the radioaerosol in the lungs. Deposition images were analyzed in terms of the inner:outer zone (I:O) ratio, a measure of deposition in an inner zone (large, central airways) vs. an outer zone (small airways and alveoli). MEASUREMENTS AND RESULTS: For the 3.68-microm aerosol, I:O ratios averaged 2.29+/-1.45 and 2.54+/-1.48 (p>0.05), indicating that aerosol distribution within the lungs was unchanged while breathing at 12+/-2 L/min vs. 31+/-5 L/min, respectively. For the 1.01-microm aerosol, I:O ratios averaged 2.09+/-0.96 and 3.19+/-1.95 (p<0.05), indicating that deposition was predominantly in the smaller airways while breathing at 18+/-5 L/min and in the larger airways while breathing at 38+/-8 L/min, respectively. CONCLUSIONS: These results suggest that the targeted delivery of an aerosol to the smaller, peripheral airways or the larger, central airways of adult CF patients may be achieved by generating an aerosol comprised of approximately 1.0-microm particles and inspiring from functional residual capacity at approximately 18 L/min and approximately 38 L/min, respectively.

Administration, Inhalation↗
PubMed2001

Foaming in simulated radioactive waste.

Radioactive waste treatment process usually involves concentration of radionuclides before waste can be immobilized by storing it in stable solid form. Foaming is observed at various stages of waste processing like SRAT (sludge receipt and adjustment tank) and melter operations. This kind of foaming greatly limits the process efficiency. The foam encountered can be characterized as a three-phase foam that incorporates finely divided solids (colloidal particles). The solid particles stabilize foaminess in two ways: by adsorption of biphilic particles at the surfaces of foam lamella and by layering of particles trapped inside the foam lamella. During bubble generation and rise, solid particles organize themselves into a layered structure due to confinement inside the foam lamella, and this structure provides a barrier against the coalescence of the bubbles, thereby causing foaming. Our novel capillary force balance apparatus was used to examine the particle-particle interactions, which affect particle layer formation in the foam lamella. Moreover, foaminess shows a maximum with increasing solid particle concentration. To explain the maximum in foaminess, a study was carried out on the simulated sludge, a non-radioactive simulant of the radioactive waste sludge at SRS, to identify the parameters that affect the foaming in a system characterized by the absence of surface-active agents. This three-phase foam does not show any foam stability unlike surfactant-stabilized foam. The parameters investigated were solid particle concentration, heating flux, and electrolyte concentration. The maximum in foaminess was found to be a net result of two countereffects that arise due to particle-particle interactions: structural stabilization and depletion destabilization. It was found that higher electrolyte concentration causes a reduction in foaminess and leads to a smaller bubble size. Higher heating fluxes lead to greater foaminess due to an increased rate of foam lamella generation in the sludge system.

Chemical Phenomena↗
PubMed1983

Cardiac and haemodynamic effects of enalapril.

The haemodynamic effects of enalapril were evaluated by sequential radionuclide studies in 10 patients followed for three to seven months. The pattern of response was remarkably similar to that of angiotensin antagonists and other oral converting enzyme inhibitors; it consisted of a reduction in peripheral resistance, minimal blood volume changes and no significant increase in either cardiac output or heart rate. The haemodynamic and neurohumoral responses to upright tilt remained normal, despite the lack of supine tachycardia in response to peripheral vasodilation. The pattern of response suggests that the haemodynamic effects of enalapril resulted from interference with angiotensin II (AII) generation rather than from a direct drug effect. Serial echocardiographic studies showed a significant regression in left ventricular (LV) hypertrophy in six out of seven hypertensive patients followed sequentially for three to seven months. Ventricular performance was well preserved despite the reduction in ventricular mass, as indicated by maintenance of the normal relationship of LV fractional shortening (% Sh) to LV end-systolic stress.

Animals↗
PubMed1998

Pharmacokinetics and biodistribution of genetically-engineered antibodies.

Monoclonal antibodies (MAbs), because of their inherent specificity, are ideal targeting agents. They can be used to deliver radionuclides, toxins or cytotoxic drugs to a specific tissue or malignant cell populations. Intact immunoglobulin (IgG) molecules have several practical limitations of their pharmacology; their relatively large size of approximately 150,000 daltons leads to a slow clearance from the blood pool and the body resulting in significant exposure to normal organs with limited quantities delivered to tumors. The IgG molecule shows a relatively poor diffusion from the vasculature into and through the tumor. Attempts to modify the pharmacology of the Ig molecule have classically involved the use of proteases to generate F(ab')2 and Fab' fragments with molecular weights of approximately 100,000 and 50,000 daltons, respectively. Fv fragments of IgG are one of the smallest size functional modules of antibodies that retain high affinity binding of an antigen. Their smaller size, approximately 25,000 daltons, enables better tumor penetration and makes them potentially more useful than a whole antibody molecule for clinical applications. Molecular cloning and expression of the variable region genes of IgG has greatly facilitated the generation of engineered antibodies. A single-chain Fv (scFv) recombinant protein, prepared by connecting genes encoding for heavy-chain and light-chain variable regions at the DNA level by an appropriate oligonucleotide linker, clears from the blood at much faster rate than intact IgG. The scFv fragment can retain an antigen-binding affinity similar to that of a monovalent Fab' fragment; this however, represents a relative decrease in binding affinity when compared to intact antibodies. The scFv with its faster clearance and lower affinity results in a lower percent-injected dose localizing in tumors when compared to the divalent IgG molecule. This may be adequate for imaging but probably not for therapy. The valency of the MAb fragment is critical for the functional affinity of an antibody to a cell surface or a polymeric antigen. In attempts to generate multivalent forms of scFv molecules, non-covalently linked scFv dimeric and trimeric molecules, disulfide linked dimeric scFvs, as well as covalently linked chimeric scFvs have been studied. These multivalent scFvs generally have a higher functional affinity than the monovalent form resulting in better in vivo targeting. Another way to alter the pharmacology of the scFvs is to modify its net charge. Charge-modified scFvs with desired isoelectric points (pI), have been prepared by inserting negatively charged amino acids on the template of the variable region genes. This can help to overcome undesirable elevations in renal uptake seen with most antibody fragments. In conclusion, genetic manipulations of the immunoglobulin molecules are effective means of altering stability, functional affinity, pharmacokinetics, and biodistribution of the antibodies required for the generation of the "magic bullet".

Animals↗
PubMedDate not supplied

Recent advances in childhood epilepsy.

Recent advances in pediatric epileptology are the consequence of the explosive advance of medical technology in recent years. In this manuscript, some of the major highlights of these technology driven advances will be presented. Recognition of a typical EEG spike pattern leads to the identification of benign focal epilepsy of childhood, an extremely frequent electro-clinical syndrome of excellent prognosis. The development of CT scan and particularly of high resolution MRI, has led to the easy identification of a variety of pathologies which were previously recognized only by pathologists. These include, among others, neuroblast migrational disorders, mesial temporal sclerosis, forme fruste of tuberous sclerosis, and slow growing small temporal neoplasms. PET scanning has also shown to be particularly sensitive in the detection of subtle pathological lesions, which may remain undetected by MRI. This is particularly true in infants in whom the PET scan may uncover an unsuspected focal lesion in patients with hypsarrhythmia, indicating that hypsarrhythmia may be a form of a secondary generalized epilepsy. Advances in surgical techniques have also decreased significantly the risks of callosotomies and hemispherectomies, techniques that are now widely used to improve seizure control in patients with catastrophic seizure disorders. A better understanding of neurotransmitters involved in the generation or inhibition of seizures has led to the development of a variety of new drugs which promise to improve our ability to control seizures conservatively. Finally, advances in molecular biology have also had an impact on epileptology, leading to the discovery of gene abnormalities underlying a number of epileptic syndromes.

Child↗
PubMed1993

Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography.

Parkinsonian tremor can be abolished by chronic high frequency thalamic stimulation of the ventral intermediate nucleus. We have studied six patients with unilateral Parkinson's disease. The patients had an electrode chronically implanted in the ventral intermediate nucleus of the thalamus. We measured changes in cerebral activity by positron emission tomography using an index of regional cerebral blood flow (rCBF). Each patient was scanned in three states: (i) tremor without stimulation (condition A); (ii) tremor with ineffective stimulation (condition B); (iii) tremor abolished by effective stimulation (condition C). The suppression of tremor (C compared with B) was specifically associated with a decrease of rCBF in the cerebellum, whereas the ineffective stimulation (B compared with A) induced a decrease of rCBF in homolateral cerebral cortex. The results give evidence for different contributions from cortex and cerebellum to the generation of parkinsonian tremor and suggest that tremor suppression is mainly associated with a decrease of synaptic activity in the cerebellum.

Aged↗
PubMed1991

Radionuclide diuresis pyelography.

Radionuclide diuresis renography continues to be relied upon as a major diagnostic tool to differentiate obstructive and nonobstructive hydronephrosis. Controversy continues to exist with respect to methodology and interpretation of intermediate obstructive patterns. In this study radionuclide diuresis pyelography was performed in 11 renal units with hydronephrosis and a pre-existing percutaneous nephrostomy tube in place. The procedure consisted of the introduction per kidney of 20 muc./kg. 99mtechnetium-diethylenetriaminepentaacetic acid and sterile saline as a bolus into the renal pelvis via a percutaneous nephrostomy tube to produce a volume equal to the capacity of the hydronephrotic system. The kidney was monitored with a gamma camera and computer system. Furosemide (0.3 mg./kg.) was injected intravenously halfway into a 40-minute study. The time/activity curves thus generated were relatively independent of the cortical transport phase. The 2 types of curves were accelerated and constant. Analysis of these pyelogram curves revealed a strong correlation between the presence of an accelerated clearance rate response to furosemide and hydronephrosis without obstruction in 5 of 6 renal units. A constant clearance rate response to furosemide correlated with the presence of obstruction in 4 of 5 units. These observations may indicate that diuretic pyelogram curve dynamics may reflect not only the presence or absence of obstruction but also the ability of the hydronephrotic kidney to respond to the diuretic. More experience must be accumulated to determine the conditions under which diuresis pyelography may become useful clinically.

Child↗
PubMed2001

Normative values of 99mTc-MIBI distribution in myocardium in males and females, as a basis for quantitative planar scintigraphic method for detection of coronary artery disease in patients of both sexes.

BACKGROUND: Radionuclide perfusion studies of myocardium are being performed using planar and tomographic (SPECT) procedures. The latter method enables better detection as well as assessment of localisation and severity of scintigraphically visualised perfusion defects. On the other hand, lower cost of planar procedures using 99mTc-MIBI as the tracer and their much wider availability in countries of Central and Eastern Europe could significantly increase the diagnostic potential of nuclear cardiology in this region. The aim of the study was an assessment of normal distribution of 99mTc-MIBI in the myocardium and generation of normative basis for quantitative planar scintigraphic procedure, aiming at detection of CAD in patients of both sexes. MATERIAL AND METHODS: The study was based on 250 patients. The reference (control) group consisted of 53 individuals (29 men, 24 women) with the low (< 10%) initial probability of CAD as estimated on basis of Diamond's tables. The second group included 197 patients (132 men, 65 women) with diagnosed CAD or with substantiated suspicion of its presence. In all patients of the latter group coronary angiography was performed and was used as the reference method for assessment of diagnostic efficacy of the scintigraphic procedure. RESULTS: The original own method of acquired data evaluation was based on creation of circumferential profiles of activity and on using the procedure of trend-fitting for obtaining average curves and their dispersion around the mean values. The mean profile curves were obtained for three projections (anterior, LAO 45 degrees and LAO 70 degrees ). These mean curves differed significantly between both sexes. In LAO 45 degrees projection the differences affected mostly the region of the septum and postero-lateral wall of the left ventricle (LV). In LAO 70 degrees projection differences were most pronounced in the antero-septal wall of the LV. CONCLUSION: Sensitivity, specificity and accuracy of CAD detection using the elaborated method, taking into account inter-sex differences, amounted to 86, 87 and 86% respectively in males, and correspondingly 81, 84 and 83% in females. The differences between corresponding indices for two sexes were statistically insignificant. For the whole group of patients the sensitivity, specificity and accuracy was 85, 86 and 85%, respectively.

Journal Article↗
PubMed1996

Radiation impact from lignite burning due to 226Ra in Greek coal-fired power plants.

Lignite contains naturally occurring radionuclides arising from the uranium and thorium series as well as from 40K. Lignite burning is, therefore, one of the sources of technologically enhanced exposure to humans from natural radionuclides. Emissions from thermal power stations in gaseous and particulate form contain radioisotopes, such as 226Ra, that are discharged into the environment causing radiation exposures to the population. About 11,672 MBq y-1 of 226Ra are discharged into the environment from four coal-fired power plants totalling 3.62 GW electrical energy in the Ptolemais Valley, Northern Greece, in which the combustion of 1.1 x 10(10) kg of lignite is required to produce an electrical energy of 1 GW y. The collective committed equivalent dose to lung tissue per unit power generated resulting from atmospheric releases of 226Ra was estimated to be 1.1 x 10(-2) person Sv (GW y)-1; i.e. more than 15 times higher than the average value for a modern type coal-fired power plant according to the UNSCEAR 1988 data.

Coal↗
PubMed1991

Renal studies in nuclear medicine.

Research in nephrologic nuclear medicine is presently concentrated in two well-defined areas: interventional procedures and the use of mercaptoacetyltriglycine. The ongoing evaluation of mercaptoacetyltriglycine continues to be a source of interesting research activity, with the distribution volume and the extent of hepatic excretion remaining points of discussion. This tracer permits quantitative determination of renal function. As an imaging agent, mercaptoacetyltriglycine compares favorably with hippurate and with diethylenetriamine penta-acetic acid, particularly in evaluating renal insufficiency. Renal function studies obtained during pharmacologic or physiologic intervention dominate research in hypertension and obstructive uropathy. Angiotensin-converting enzyme inhibition improved the renographic detection of renovascular lesions. Interventional renography with angiotensin-converting enzyme inhibition or ergometric exercise were both capable of generating useful prognostic data on the posttherapy blood pressure response in patients with renovascular hypertension. Interventional diuretic renography with furosemide permits surgical intervention to be reserved for organs at immediate risk because the degree of obstruction and the extent of renal function compromise are easily recognized.

Blood Pressure↗
PubMed1976

In vitro stabilization of a low-tin bone-imaging agent (99mTc-Sn-HEDP) by ascorbic acid.

The presence of oxidants in the 99mTc-pertechnetate and of oxygen in diagnostic kits containing low concentrations of Sn(II) has a detrimental effect upon in vitro and in vivo stability. Maintaining a nitrogen atmosphere or increasing the Sn(II) concentration inhibits the formation of 99mTcO4-. However, the latter remedy is likely to cause uptake in the reticuloendothelial system and has been associated with false positive or negative brain scans. We used ascorbic acid (an antioxidant) to ensure the in vitro stability with the low-Sn(II) bone agent disodium etidronate. In vitro stability studies by instant thin-layer chromatography, using high-acitivity generators and "instant pertechnetate," yielded less than 2% free pertechnetate at 24 hr after preparation. Distribution studies in guinea pigs show neither altered distribution of the bone agent nor abnormal distribution of ascorbic acid, suggesting its sole function as a noncomplexing stabilizer.

Animals↗
PubMed2000

Rhenium-188-HEDP in the palliative treatment of bone metastases.

INTRODUCTION: Rhenium-188-HEDP (188Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of bone pain due to metastases. As a product of a 188W/188Re generator it is convenient for clinical use. With a short physical half life of 16.9 hours and a maximal beta-energy of 2.1 MeV, it is suitable for therapy. METHODS: We investigated the influence of 188Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 15 patients. All patients were interviewed using standardized questions before, and 1, 2, 3, 4, 8, and 12 weeks after therapy. Blood samples were drawn weekly for 12 weeks, and a blood count was performed. Patients underwent gamma camera imaging to determine the radionuclide accumulation 4, 20, and 28 hours after therapy. The patients were treated with 1600 to 3459 MBq of 188Re-HEDP. RESULTS: Patients showed an improvement of the Karnofsky performance index from 74 +/- 8% to 84 +/- 11% 12 weeks after therapy. This improvement was statistically significant (p = 0.001). Eighty percent of the patients described pain relief and reduction of analgesics. Twenty percent of the patients could discontinue their analgesics. Mean platelet count decreased from (284 +/- 84)*10(3)/microliter to (205 +/- 62)*10(3)/microliter, and mean leukocyte count from (7.5 +/- 1.5)*10(3)/microliter to (5.9 +/- 2.1)*10(3)/microliter after therapy. The maximal differences between the values of platelets and leukocytes before and after therapy were not statistically significant (p = 0.021 and p = 0.094). Prostate specific antigen decreased from 95 +/- 83 ng/ml to 41 +/- 21 ng/ml, the difference was not statistically significant (p = 0.443). The bone accumulation 4, 20, and 28 hours after therapy was 1.3 +/- 0.5%, 0.6 +/- 0.3%, and 0.45 +/- 0.2% of the injected dose of a single metastasis, and 57 +/- 17%, 15.5 +/- 2% and 11 +/- 3% in the whole body, respectively. The effective half-life of 188Re-HEDP was 15.3 +/- 3.0 hours in the bone metastases, and 11.4 +/- 2.8 hours in the whole body. This corresponds to a residence time of 0.22 +/- 0.25 hours in the bone metastases, and of 10.54 +/- 2.59 hours in the whole body. CONCLUSION: In a small patient population, 188Re-HEDP therapy for bone pain palliation was effective and was associated with minimal toxicity.

Aged↗