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At least 469 records · Page 26Linked to original sources
PubMed2001

Antibody constructs for radioimmunodiagnosis and treatment of human pancreatic cancer.

Pancreatic cancer (PC) is a common disease that is seldom cured. Current approaches to the treatment of PC are not effective because the non-specific nature of both chemotherapy and external beam radiation results in toxicity to normal tissue. Monoclonal antibodies (MAbs) can be used as selective carriers for delivering radionuclides, toxins, or cytotoxic drugs to malignant cell populations. Therefore, MAb-technology has led to a significant amount of research in targeted therapy. Targeted therapy would generally allow the concentration of cytotoxic agents in tumors and would markedly lessen the toxicity to normal tissues, which limits the dosage and effectiveness of systemically administered drugs. A variety of MAbs are being pre-clinically evaluated for the diagnosis and treatment of PC. Novel recombinant antibody constructs hold a promising future in both the diagnosis and treatment of cancer. By genetic-engineering methods, several high affinity antibody fragments with optimum tumor targeting properties, such as higher functional affinity (divalent and multivalent scFvs) and blood residence time (good tumor localization with high radiolocalization index), have been generated. Animal models have permitted the in vivo assessment of these antibody-based reagents, therapeutic/diagnostic radionuclide, radiolabeling conditions, and efficacy of administration regimes. For PC, immunoscintigraphy using MAbs has taken new strides. The use of MAbs and their fragments for radioimmunoguided surgery and therapy of PC has shown encouraging results at preclinical levels and warrants further attention.

Adenocarcinoma↗
PubMed2000

Effect of geological processes on coal quality and utilization potential: review with examples from western Canada.

This review article compares the elemental and radionuclide concentrations in coals from western Canada, the vast majority of which are used for power generation in Alberta. The coals range in age from lower Cretaceous to middle Eocene, and in rank from subbituminous to high volatile bituminous. Some of the coals were deposited in deltaic lagoonal to marine settings while others formed under lacustrine conditions in intermontane graben settings or in alluvial plains. The role of source rock (provenance), depositional environment, tectonic regime and hydrologic conditions on elemental concentration and distribution will be discussed, with specific examples from western Canada. In addition, the effect of natural weathering, igneous intrusion and self-burning (spontaneous combustion) on the enrichment and/or depletion of elements will be presented. The emphasis throughout this review article will be on the fate of elements of environmental concern and interest (e.g. As, Ba, B, Cl, Co, Cr, Cu, Mn, Mo, Se, Th, U, V and Zn) and of radionuclides of the U and Th series upon coal utilization. This article is also intended for those not familiar with the geological or environmental sciences, particularly as related to fossil fuel utilization.

Alberta↗
PubMed1988

Early diagnosis and treatment of pancreas allograft rejection.

A major problem in vascularized pancreas transplantation is the lack of reliable methods for the early diagnosis and effective treatment of allograft rejection. Over a 2-year period, 54 rejection episodes occurred in 31 patients (13 isolated pancreas, 18 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 253 radionuclide pancreas examinations were performed (mean 8.4 per patient) utilizing 99mtechnetium-DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft caused the technetium index (TI). Rejection episodes were characterized as isolated pancreas (22), combined pancreas-kidney (16), or isolated renal (16) allograft rejection in combined engraftments. The majority of rejection episodes occurred early (within 3 months of transplant, N = 47) and were more responsive than late rejection to anti-rejection therapy (89.4% vs 42.9%, P = 0.01). Mean urinary amylase (UA) levels and TI during normal allograft function were 29,398 U/l and 0.55%, while levels heralding rejection were 6,528 U/l and 0.40%, respectively (P less than 0.05). The treatment of rejection based upon renal dysfunction or combined renal and pancreas dysfunction resulted in significantly higher graft salvage with a lower incidence of hyperglycemia when compared to isolated pancreas allograft rejection. Of the 11 patients who developed hyperglycemia, 8 (72.7%) ultimately lost their pancreas grafts (P less than 0.001). Following therapy, a TI above 0.3% was associated with 97.4% graft survival, while levels below 0.3% resulted in a 70% rate of graft loss (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1989

Early detection of rejection in pancreas transplantation.

A major dilemma in pancreas transplantation is the lack of reliable methods for the early detection of allograft rejection. Over a 26-mo period, 70 rejection episodes occurred in 36 patients (13 isolated-pancreas, 23 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 300 radionuclide pancreas examinations were performed (mean 8.3/patient) utilizing 99mTc-labeled DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft (technetium index, TI). Rejection episodes were defined as isolated pancreas, isolated kidney, or combined pancreas-kidney. Mean urinary amylase (UA) levels and TI during normal allograft function were 30,256 U/L and 0.57%, respectively, whereas levels heralding rejection were 6873 U/L and 0.39% (P less than .05). The treatment of rejection based on kidney dysfunction or combined pancreas-kidney dysfunction resulted in significantly higher graft salvage and a lower incidence of hyperglycemia compared with isolated-pancreas-allograft rejection. After therapy, a TI greater than 0.3% was associated with 95.9% graft survival, whereas levels less than 0.3% resulted in a 72.7% rate of graft loss (P less than .001). Similarly, pancreas allografts with a UA greater than 10,000 U/L had 92.2% functional survival, whereas levels less than 10,000 U/L resulted in a 53.3% rate of graft loss (P less than 0.001). Overall, reversal of rejection occurred in 80% of cases, with 10 pancreas and 2 kidney allografts lost due to rejection. Monitoring pancreas-allograft function by UA, TI, and renal function in simultaneous transplants allows for the timely diagnosis and successful treatment of pancreas-allograft rejection.

Adult↗
PubMedDate not supplied

[Formation and migration of radioactive microemboli to the lung during radiovenography].

Two patients with lower extremity thrombophlebitis were studied by radionuclide venography with macroaggregated albumin labelled with 99mTc. Data analysis was performed with a new method. It generated sequential series of imagen (1-2 sec/frame) of the transit of the tracer through leg, thigh, and abdomen, allowing a more precise definition of temporal changes on regional radioactivity. This method rendered the first real evidence of the binding of the tracer to pre-existent venous thrombi, of the dislodgement of these and their gradual fragmentation during their transit to the lungs. The patients had no complaints during or after the study. Lung scanning, performed 24 hours later, showed slight alteration on regional lung perfusion in one case, and none in the other. It is concluded that radioactive microemboli to the lungs is a minor complication of radionuclide venography, which does not justify prevention. This could only nullify the sensitivity of the procedure.

Adult↗
PubMed1996

Studies on the long-term stabilities of the background of radionuclides in inductively coupled plasma mass spectrometry (ICP-MS)A review of radionuclide determination by ICP-M.

The long-term stabilities of the ICP-MS background of nine radionuclides are studied, of which the signals are partially superimposed by polyatomic interferences or affected from carry-over and memory effects. The background generated by the ICP flame, by two pure waters, and by nitric acid (2% v/v) was investigated in detail. A minimum of 50 measurement points was used for each long-term investigation. The detection limits of the radionuclides of the masses 90 amu ((90)Sr: 30 Bq/mL), 99 amu ((99)Tc: 4 mBq/mL), 238 amu ((238)U: 10 nBq/mL), and 244 amu ((244)Pu: 0.6 microBq/mL) are calculated from the mean standard deviation of the background signals. For all nine radioisotopes, the calculated detection limits are between 0.8 and 6 pg/mL. While the detection limit of the mass 90 amu is blank limited, those of the mass 99 amu and the actinides are totally uneffected by the blank solutions. The detection limits are compared with those given in literature.

Journal Article↗
PubMed1993

Normal right ventricular systolic and diastolic function assessed by krypton-81m equilibrium ventriculography.

Krypton-81m equilibrium ventriculography was used to study right ventricular function in 23 healthy male volunteers. Technetium-99m lung perfusion scintigraphy was employed to subtract radionuclide activity within lung during image analysis thereby enhancing image quality. The imaging technique was used to generate a time-activity curve for the right ventricle allowing the definition of indices of normal systolic and diastolic function for the right ventricle. At rest, indices of systolic ejection and diastolic filling were comparable to those previously reported for the left ventricle. Using the imaging technique, movement artifact during exercise reduces image quality and limits accurate measurement of these indices to resting studies.

Adult↗
PubMed2005

Cancer radioimmunotherapy with alpha-emitting nuclides.

In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with beta-emitters for the treatment of refractory cases. The development of novel RIT with alpha-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with alpha-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of alpha-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an alpha-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with alpha-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of alpha-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.

Alpha Particles↗
PubMed1995

Technetium-99m chelators in nuclear medicine. A review.

Nuclear medicine is a branch of medical imaging that uses radioactive tracers to examine the function of body systems. The radionuclide used in about 90% of all examinations is 99Tcm, which is available from 99Mo/99Tcm generators at most nuclear medicine departments. In aqueous medium, technetium is chemically stable as pertechnetate, 99TcmO4-. Injected into the human body, pertechnetate will be absorbed by the thyroid gland because of the similarity to iodide in its radius and charge. To reach targets in the human body other than glandula thyreoidea, 99Tcm needs a carrier molecule, usually a chelating agent. Many chelators that form stable complexes with 99Tcm have affinities for certain tissues in the human body. Other chelators can be manipulated by pharmaceutical formation to be retained in certain body systems. In order to form bonds with technetium, the chelator must contain electron donors like nitrogen, oxygen and sulfur. Space between multiple electron donor atoms is required to allow several bonds to form with the central metal. The stability of the complex increases with increasing number of bonds. Today, chelators for the use with 99Tcm exist for a number of highly sensitive scintigraphic studies of the brain, heart, skeleton, kidneys, hepatobiliary system and lungs. This includes chelators such as dimercaptosuccinic acid, 1,2-ethylenediylbis-L-cysteine diethyl ester, methylenediphosphonate, hexamethylpropyleneamineoxime and hexakis(methoxy isobutyl isonitrile).

Chelating Agents↗
PubMed1994

Pulsed-field gel electrophoretic analysis of DNA double-strand breaks in mammalian cells using photostimulable storage phosphor imaging.

Double-strand break (dsb) induction and repair was determined in the human colon carcinoma cell line clone A using pulsed-field gel electrophoresis (PFGE) coupled with photostimulable storage phosphor imaging technology. Because 14C-radioactivity was measured in a dried agarose gel following electrophoresis, no laborious processing of the gel, cutting out regions of interest, liquid scintillation counting, etc., was necessary thereby saving labour, time and cost. The signal generated by phosphor screens was linear over 5 logs and sensitive to low levels of radionuclide exposure. Migration of broken DNA into the gel upon electrophoresis was determined to be log-linear as as a function of dose, and dsb rejoining after irradiation could be measured for exposures as low as 5 Gy. The kinetic parameters of dsb rejoining are independent of the initial dose delivered within experimental error over the range of 5-20 Gy and complete after 4 h of recovery. The use of photostimulable storage phosphor imaging allows the use of low levels of radionuclide incorporation for DSB analysis in radiosensitive mammalian cells that would not be possible by other methods.

Colonic Neoplasms↗
PubMed1975

Technetium-99m: basic nuclear physics and chemical properties.

The nuclear physics and chemical properties of technetium-99m are reviewed. The review of basic nuclear physics includes: classification of nuclides, nuclear stability, production of radionuclides, artificial production of molybdenum-99, production of technetium 99m and -99Mo-99mTc generators. The discussion of the chemistry of technetium includes a profile of several -99mCc-labeled radiopharmaceuticals.

Aluminum↗
PubMed1988

[Quantitative study of mucociliary clearance using static scintigraphy].

Mucociliary clearance can be evaluated by radionuclide techniques, but such approaches have been usually implemented only in research-oriented laboratories because of technical difficulties. A very practical radionuclide method is here presented which requires only three static acquisitions after the inhalation of a polydisperse radioaerosol produced by a commercial generator. Data processing is also very simple. The diagnostic performance of the method was tested on a study population of 10 healthy subjects and 10 patients with atrophic bronchitis; a highly significant difference between normal and pathological patients was found. Its simple implementation and diagnostic yield recommend this radionuclide method for the routine assessment of mucociliary clearance also in busy clinical-oriented laboratories.

Adult↗
PubMed2004

Multimodality noninvasive imaging of gene transfer using the human sodium iodide symporter.

UNLABELLED: In this study we investigated the feasibility of using radionuclide accumulation mediated by the human sodium iodide symporter (hNIS) gene in conjunction with various imaging modalities as a reporter system to noninvasively monitor the expression of transgenes delivered for gene therapy. METHODS: NIS-expressing adenovirus (Ad-hNIS) was delivered in vitro to MB-435 breast carcinoma cells. NIS-mediated accumulation of (125)I(-), (99m)TcO(4)(-), and (76)Br(-) by the cells was visualized using autoradiography, gamma-camera scintigraphy, and PET imaging, respectively. RESULTS: For all imaging modalities, signal intensity generated by the cells correlated linearly both with the amount of Ad-hNIS and with the activity of radionuclide added to the cells. CONCLUSION: hNIS-mediated cellular accumulation of radionuclide was clearly visualized by all 3 imaging modalities tested. This preliminary study demonstrates the feasibility of using hNIS for monitoring the location and magnitude of expression of genes delivered during gene therapy.

Breast Neoplasms↗
PubMedDate not supplied

Intranasal deposition of nebulized saline: a radionuclide distribution study.

BACKGROUND: Despite the popularity of various nasal sprays and nebulizers, there are limited data regarding the anatomic distribution of particles generated by these devices. This pilot study sought to characterize distribution patterns of nebulized and sprayed saline particles in normal subjects and postsurgical sinus patients. METHODS: Fifteen subjects were studied in three trials: metered-dose nasal spray bottle versus vortex-propelled nebulizer in normal subjects, passive-diffusion nebulizer versus vortex nebulizer in normal subjects, and passive nebulizer versus vortex nebulizer in postsurgical sinus patients. Radiolabeled saline was administered, and nose, lungs, and stomach were imaged. Images were scored by four blinded reviewers for degree of penetration at nine anatomic subsites. RESULTS: Compared with spray bottle, the vortex nebulizer showed more focal intranasal distribution with reduced nasopharyngeal, pharyngeal, and gastric penetration in normal subjects. Three of five subjects showed probable frontal sinus penetration by vortex nebulizer, but no other sinus penetration was noted. No patients showed sinus penetration with the spray bottle. In a separate trial against the passive nebulizer, the vortex nebulizer again showed a greater tendency for sinus penetration in normal subjects, with three of five showing some degree of sphenoid penetration and one of five showing slight maxillary penetration. In contrast, no sinus penetration was observed with the passive nebulizer. In the postsurgical patient cohort, minimal sinus penetration was noted with either the vortex nebulizer or the passive nebulizer. Despite surgically patent sinuses, only one of five subjects showed any type of sinus penetration. CONCLUSION: The nebulizer and nasal spray devices tested in general showed limited penetration of the sinuses in both normal and postoperative patients. The device showing greatest promise for sinus penetration in normal patients was the vortex nebulizer, with an overall penetration rate in normal patients of 30% in the frontal, 30% in the sphenoid, and 10% in the maxillary. Understanding delivery patterns of topical therapies may be important in evaluating the efficacy of various topical treatment modalities.

Equipment Design↗
PubMed1992

Left ventricular diastolic function in systemic sclerosis: assessment by radionuclide angiography.

The aim of this study was to assess left ventricular function in subjects with systemic sclerosis. Twenty-four women with systemic sclerosis (mean age 48 +/- 11 yr) and 14 age- and sex-matched normal subjects were studied by radionuclide angiography performed at rest with a temporal resolution of 20 msec/frame. Left ventricular volume curves were generated and indices of systolic and diastolic function were computed. Left ventricular diastolic asynchrony was evaluated by dividing the left ventricle into five regions and then computing the time-to-peak filling rate for each region. After excluding the valvular region, the coefficient of variation of this index was obtained. The isovolumic relaxation period was prolonged in systemic sclerosis patients in comparison to normal subjects (127 +/- 39 msec versus 87 +/- 44 msec, p less than 0.05). Moreover, 38% of the systemic sclerosis patients had a subnormal peak filling rate. Left ventricular diastolic asynchrony was increased in the systemic sclerosis group, as expressed by a higher coefficient of variation of the regional time to peak filling rate (27.9% +/- 11.5% versus 14.5% +/- 8.6%, p less than 0.05). Our results indicate an impaired relaxation and an increased diastolic asynchrony in patients with systemic sclerosis.

Female↗
PubMed1985

Early detection of diastolic impairment in long-standing hypertension by a noninvasive volume challenge method.

A simple, easily reproducible, noninvasive, provocative test for the assessment of early diastolic impairment in long-standing hypertension is presented. Volume challenge of the heart was produced by elevating the subject's legs to 45 degrees for 5 minutes, thus increasing the venous return to the right heart. Using gated radionuclide ventriculography and Fourier analysis, the atrial structures were delineated and time-activity curves were generated. Early diastolic emptying slope of the left atrium was used to assess left ventricular compliance changes in hypertensives. The left atrial early diastolic emptying rate was markedly reduced in 38 hypertensive patients (45.5 +/- 15.4 counts/s) when compared with 14 healthy subjects (78 +/- 16 counts/s). The legs-up procedure induced subsequent decrease in left atrial emptying rate in patients with long-standing hypertension and left ventricular hypertrophy (-27.4 +/- 11%). In patients with recent onset hypertension there was a depressed early diastolic emptying rate (55.79 +/- 10 counts/s), but a "normal" response to the legs-up procedure (an increase in left atrial emptying rate: 12.84 +/- 7%). Global ejection fraction was normal in all subjects studied, decreasing after induction of augmented venous return in long-standing hypertension. Reduction in left atrial early diastolic emptying rate, caused by the legs-up manoeuvre appears to be an early and sensitive indicator of the left ventricular diastolic impairment in essential hypertension.

Blood Volume↗
PubMed1994

Prediction of runoff transport of fallout 90Sr.

A model is described for the prediction of runoff transfer of fallout 90Sr without recourse to long-term measurements. The values of model parameters can be readily established from few field measurements of the solid/solution partitioning of 90Sr and a natural, atmospherically delivered radionuclide such as 210Pb, and the usually well documented fallout and hydrologic data. The model-generated profiles of 90Sr for two major Canadian watersheds compare favorably to those established through long-term monitoring of receiving waters.

Forecasting↗
PubMed1996

Complete decay of radionuclides: implications for low-level waste disposal in municipal landfills.

The time required for the complete decay of a radioactive source can be quantified by specifying an acceptable probability and using an original derivation. The physical phenomenon of complete decay may be used as the technical basis to change regulations and permit, with public acceptance, the inexpensive disposal of short half-lived radioactive waste into municipal landfills. Current regulations require isolation of trash from the biosphere for 30 years during the post-closure control period for municipal landfills. Thirty years is sufficient time for complete decay of significant quantities of short-lived radionuclides, and there is a large decay capacity in the nation's landfills. As the major generators of low-level radioactive waste with relatively short half-lives, the academic, medical, and research communities likely would benefit most from such regulatory relief. Disposal of such waste is prohibited or costly. The waste must be specially packaged, stored, transported, and disposed in designated repositories. Regulatory relief can be initiated by citizens since the Administrative Procedures Act gives citizens the right to petition for regulatory change.

Radioactive Waste↗