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Biomedical subjects

F Brady

Publications and source records attributed to F Brady.

At least 37 records · Page 2Linked to original sources
PubMed1996

Evaluation of [11C]RTI-121 as a selective radioligand for PET studies of the dopamine transporter.

The cocaine analogue RTI-121 (3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester), when labeled with carbon-11, was evaluated in rats as a potential PET ligand for the dopamine transporter. The compound gave in vivo striatum:cerebellum ratios that were similar to those obtained with the related ligand [11C]RTI-55 (2 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester) but showed a much greater selectivity for the dopamine compared with the 5-HT uptake site. The results indicate that [11C]RTI-121 could be used in preference to [11C]RTI-55 in man. Experimentally, [11C]RTI-121 has potential in the quantification of dopamine terminal function in rat models of disease, using a combination of autoradiography, postmortem sampling, and in vivo tomography.

Animals↗
PubMed1996

Anticipation of coincidence, gender, and sports classification.

This study investigated the effects of sport classification and gender on anticipation of coincidence. 102 undergraduate male and female students from open skills, closed skills, and nonathletic groups were tested on the Bassin Anticipation Timer. The dependent measures of absolute error, constant error, and variable error were analyzed in a 2 (gender) x 3 (sport classification) x 4 (speeds) design. Men had lower absolute and constant error scores than women. Open skills athletes were less variable in their responses while male open skills athletes were more accurate and less variable at the faster speeds. Performance on the Bassin Anticipation Timer may not be representative of athletic skills.

Adult↗
PubMed1995

Sports skill classification, gender, and perceptual style.

This study was designed to examine the relationship of sport classification and gender to perceptual style. 102 male and female undergraduate students from open-skilled, closed-skilled and nonathletic groups were administered the Rod and Frame Test and the Embedded Figures Test. Analysis of variance indicated men to be more field independent than women on the Rod and Frame Test, while there were no gender differences on the Embedded Figures Test. Athletes performing open and closed skills scored significantly more field independent on the Rod and Frame Test than the nonathletes. There were no significant differences among the groups on the Embedded Figures Test. No correlation between the two measures of perceptual style was obtained.

Adult↗
PubMed1993

Candidate recombinant vaccine for human B19 parvovirus.

Recombinant baculoviruses were used to produce human B19 parvovirus empty capsids composed of only VP2 and VP2 capsids containing 4%, 25%, 35%, or 41% VP1 protein. Immunogenicity of the purified capsids, formulated with or without adjuvant, was evaluated in mice, guinea pigs, and rabbits. Sera were analyzed for total anti-B19 parvovirus antibodies, antibodies specific to the region unique to the VP1 capsid protein, and virus neutralizing antibodies. A relationship was observed between the development of antibodies specific to sequences unique to the VP1 protein and virus neutralization. The polypeptide composition of the empty capsid immunogens appeared to be important for elicitation of potent virus neutralizing activity. VP2 capsid immunogens devoid of VP1 protein, or consisting of only 4% VP1, the composition of naturally occurring virions, were generally poor at eliciting high levels of virus neutralizing activity. Capsids consisting of > or = 25% VP1 protein efficiently and consistently provoked vigorous B19 virus neutralizing responses. Recombinant empty capsids enriched for the VP1 protein should serve as the basis for a human B19 parvovirus vaccine.

Aluminum Hydroxide↗
PubMed1993

Generation of neutralizing anti-B19 parvovirus human monoclonal antibodies from patients infected with human immunodeficiency virus.

The prevalence of IgG antibodies to human B19 parvovirus (anti-B19) is elevated in individuals infected with human immunodeficiency virus (HIV), especially during the later stages of HIV infection. In subjects with high titers of IgG anti-B19, 86% (19 of 22) had circulating B cells producing anti-B19. Immortalization of these cells with Epstein-Barr virus and generation of heterohybridomas by fusion with a mouse X human heteromyeloma resulted in the production of two cell lines producing IgG1 kappa monoclonal antibodies (MAbs). Both of these MAbs were specific for conformational epitopes on the VP2 capsid protein of B19 parvovirus and both were capable of neutralizing 50% of the viral infectivity in a human erythroid colony-forming unit assay at < or = 1 micrograms of MAb/mL. These human MAbs are potentially useful in the treatment of acute B19 parvovirus infection.

Antibodies, Monoclonal↗
PubMed1993

In vivo quantification of pulmonary beta-adrenoceptor density in humans with (S)-[11C]CGP-12177 and PET.

The in vivo regional distribution of pulmonary beta-adrenoceptors was imaged and quantified in humans with the hydrophilic beta-adrenoceptor antagonist (S)-CGP-12177 labeled with carbon-11 [(S)-[11C]CGP-12177] and positron emission tomography (PET). Six normal male volunteers and eight patients with hypertrophic cardiomyopathy were studied. PET scanning consisted of transmission (tissue density), C15O (blood volume), and (S)-[11C]CGP-12177 (beta-adrenoceptor) emission scans. High-specific-activity (S)-[11C]-CGP-12177 (7.1 +/- 2.0 micrograms, 6.5 +/- 2.1 GBq/mumol) was given intravenously followed by a low-specific-activity (S)-[11C]CGP-12177 injection (34.0 +/- 4.8 micrograms, 2.3 +/- 0.8 GBq/mumol). Binding capacity (Bmax) was calculated in each region of interest as picomoles per gram by normalizing it to the local extravascular tissue density. In normal subjects, average Bmax for all regions of interest was 14.8 +/- 1.6 (SD) pmol/g, which is similar to previously reported in vitro values. In both groups there were no differences in beta-adrenoceptor density between peripheral and central regions nor between right and left lungs. In patients with hypertrophic cardiomyopathy, extravascular tissue density was 24% higher than in normal subjects; Bmax per milliliter thoracic volume was correspondingly higher but was not different from that in normal subjects when expressed per gram tissue (15.8 +/- 2.6 pmol/g). These data suggest that in vivo beta-adrenoceptor density may be quantifiable in humans with the use of PET. This should offer a means to study physiological regulation through repeat measurements.

Adrenergic beta-Antagonists↗
PubMed1993

New techniques in the pharmacokinetic analysis of cancer drugs. IV. Positron emission tomography.

Positron emission tomography is a powerful tool for the absolute quantification of injected positron emitting radiotracer concentration within tissues in vivo. Very detailed spatiotemporal data can be obtained without biopsy sampling. Most chemotherapeutic agents can be labelled with a positron emitter, and human tissue and tumour pharmacokinetics can be obtained non-invasively. Its main limitations are the inability to discriminate metabolites, the short half-life of the isotopes used and the specialized equipment required. Despite this, PET has the potential to make a major contribution in the study of the pharmacokinetics of anti-cancer drugs.

Antineoplastic Agents↗
PubMed1991

Asymmetric synthesis of a precursor for the automated radiosynthesis of S-(3'-t-butylamino-2'-hydroxypropoxy)-benzimidazol-2-[11C]one (S-[11C]CGP 12177) as a preferred radioligand for beta-adrenergic receptors.

S-[1-(2,3-Diaminophenoxy)]-3'-(N-t-butylamino)propan-2'-ol has been synthesized in three steps from 2,3-dinitro-phenol and the chiral auxiliary, S-glycidyl-3-nitrobenzenesulphonate, to provide a precursor for labelling S-(3'-t-butylamino-2'-hydroxypropoxy)-benzimidazol-2-one (S-CGP 12177) with the short-lived positron-emitting radionuclide, carbon-11 (t 1/2 = 20.4 min; beta+ = 99.8%). Reaction of the diamine with [11C]phosgene, itself derived from no-carrier-added cyclotron-produced [11C]methane, provides radiochemically and chemically pure S-[carbonyl-11C]CGP 12177 in greater than 95% enantiomeric excess after HPLC. Automated apparatus is described for safely producing up to 5.9 GBq (160 mCi) of S-[11C]CGP 12177 with high sp. act. (20-40 GBq/mu mol or 0.54-1.08 Ci/mu mol) in a form suitable for human intravenous injection at only 30 min from the end of radionuclide production. S-[11C]CGP 12177 is preferred to the formerly described racemate as a radioligand for the study of beta-adrenergic receptors in vivo by positron emission tomography.

Adrenergic beta-Antagonists↗
PubMed1989

Feasibility study of fluorine-18 labeled dopa for melanoma imaging.

Feasibility of fluorine-18 labeled L-dopa for melanoma imaging was investigated. In B16 melanoma-bearing mice given 2-[18F]fluoro-L-dopa, the radioactivity in the B16 decreased for the first 60 min and then remained constant, while all other tissues investigated decreased with time. High tumor uptake ratios for all other tissues except for the pancreas were obtained at 120 min. 6-[18F]Fluoro-L-dopa showed a similar tissue distribution. However, the B16 uptake was about half that value for the 2-fluoro analogue. A higher incorporation rate of 2-[18F]fluoro-L-dopa into the acid-precipitable fraction of the melanoma also showed that the 2-[18F]fluoro-L-dopa was a preferable melanin precursor. Among the four kinds of non-melanoma tumors in mice or rats three tumors showed an uptake of 2-[18F]fluoro-L-dopa similar to the B16 at 60 min. However, larger melanoma-to-tissue uptake ratios were observed when compared to non-melanoma tumors.

Animals↗
PubMed1987

Animal and human studies of a new 99mTc labelled phosphine-isocyanide complex with possible applications to radionuclide ventriculography.

A new 99mTc-phosphine-isocyanide complex with the general structure [99mTc (DEPE)2(CNR)2]+ has been synthesised and tested in animals and one human. In three animal species (rat, rabbit, dog), the complex is an efficient myocardial imaging agent, while in humans it remains in the blood pool. The complex is 100% protein bound in animals and humans, but whereas in humans it is attached to a 51.5 kdalton protein (probably prealbumin), in rabbits it appears to be bound to a larger macromolecule (M.W. greater than 100 kdalton). The efficiency of the complex for blood pool labelling was tested in a human volunteer and compared with the standard in vivo red cell labelling technique with stannous pyrophosphate. A satisfactory radionuclide angiogram could be performed with less than 370 MBq of the complex. The count rate for the complex (cps/MBq) was 15% higher than that obtained with the labelled red cells and the absence of splenic activity was notable. In humans this complex appears to be an efficient blood pool labelling agent which might be useful for radionuclide ventriculography.

Animals↗
PubMed1987

Preparation of [11C]buprenorphine--a potential radioligand for the study of the opiate receptor system in vivo.

A method is described for the preparation of [11C]buprenorphine in high specific activity, based on the reaction of N-(de-cyclopropylmethyl)buprenorphine with "no carrier added" [1-11C]cyclopropanecarbonyl chloride followed by reduction with lithium aluminium hydride. The [1-11C]cyclopropanecarbonyl chloride is itself prepared from cyclotron-produced [11C]carbon dioxide. The overall preparation time is 57 min from the end of radionuclide production, and the radiochemical yield is ca 20%, (decay-corrected from [11C]-carbon dioxide). [11C]Buprenorphine has potential as a radioligand for the study of the opiate receptor system in vivo by means of position emission tomography.

Animals↗
PubMed1986

A comparison between regional cerebral blood flow measurements obtained in human subjects using 11C-methylalbumin microspheres, the C15O2 steady-state method, and positron emission tomography.

Regional cerebral blood flow (rCBF) values were measured in nine normotensive subjects with known previous myocardial infarctions using 15 mu 11C-methylalbumin microspheres and positron emission tomography (PET). Microspheres were injected directly into the left ventricle of each subject during routine cardiac angiography and blood flow calibrated using the reference sample technique. rCBF values were compared with those obtained for a group of fifteen age-matched normal controls using the C15O2 steady-state inhalation technique. Using 1 cm radius circular regions of interest, the 11C-microspheres approach yielded mean blood flow values of 51 ml/100 ml/min and 48 ml/100 ml/min for regions of interest dominated by temporal and frontal cortical grey matter respectively. An rCBF value of 32 ml/100 ml/min was obtained for regions of interest dominated by frontal white matter. Mean rCBF values obtained for these regions using the C15O2 method were not significantly different (52 ml/100 ml/min, 44 ml/100 ml/min, and 28 ml/100 ml/min respectively), but the C15O2 approach gave a significantly lower rCBF value than the 11C-microspheresfor regions of interest dominated by occipital grey matter. Although the two groups of subjects studied were not strictly equivalent, the good agreement between blood flow values obtained using the 11C-microspheres and the C15O2 techniques is of interest, and suggests that the assumptions of the C15O2 steady-state approach do not lead to large errors in practice.

Aged↗
PubMed1986

Regional myocardial and organ blood flow after myocardial infarction: application of the microsphere principle in man.

A physiologic means of measuring the distribution of cardiac output and regional myocardial blood flow has been developed that uses human albumin microspheres labeled with carbon-11 (11C) and external detection with positron emission tomography. Ten patients with previous myocardial infarction were studied to investigate the level of blood flow in normal and infarcted segments of the heart. After diagnostic catheterization, 4 to 6 mCi of 11C on 2 to 3 million sterile microspheres (15 to 20 micron) were mixed and injected into the apex of the left ventricle during timed withdrawal of arterial blood to obtain reference flow values. Regional activity in brain, heart, lungs, liver, spleen, and kidneys was measured tomographically. Blood flow was calculated based on the relationship between total activity in a reference flow and tissue activity in tomograms of each organ (ml/min/100 g). No adverse effects were noted after injection of the microspheres. Successive myocardial tomograms showed no loss of activity. There were no significant differences in flow values in matched regions of paired organs. Mean cerebral flow was 52.4 +/- 10.0 ml/min/100 g in the frontal lobes, 54.4 +/- 8.8 in the temporal lobes, 67.6 +/- 8.2 in the occipital lobes, and 53.0 +/- 9.4 in the basal ganglia. Flow was 16.0 +/- 8.4 ml/min/100 g (range 0 to 40.0) in the center of infarcted myocardium and 82.0 +/- 32.0 in the remote segments. This method meets most of the demands for use of microspheres to measure tissue blood flow. The wide range of flow values in infarcted myocardium may be a function of infarct size, spatial resolution, or pathologic evidence of islands of viable tissue. Patients with angina had high flow values in the infarcted segment, whereas those with heart failure had significantly lower values. Surviving myocardium in the region of the infarct may need to be considered if patients complain of angina, particularly when treatment is aimed at preserving ventricular function.

Adult↗
PubMed1984

Preparation of human serum [methyl-11C]methylalbumin microspheres and human serum [methyl-11C]methylalbumin for clinical use.

Safely-injectable suspensions of human serum [methyl-11 C] methylalbumin microspheres have been prepared via the reaction of human serum albumin microspheres with [11C]methyl iodide, itself prepared in a novel one-pot synthesis from cyclotron-produced [11C]carbon dioxide. The preparation takes only 30 min from the end of radionuclide production and proceeds in 22% radiochemical yield based on the activity of [11C]carbon dioxide used and decay-corrected. It has been shown that such microspheres are highly stable in vivo and may be used as reference blood flow markers in positron emission tomography (PET). Similarly, safely-injectable and radiochemically pure solutions of human serum [methyl-11C] methylalbumin have been prepared in 31% radiochemical yield and in 40 min from the end of [11C]carbon dioxide production via the reaction of [11C]methyl iodide with human serum albumin. This radiopharmaceutical is intended for studies of lung permeability and blood-brain barrier permeability by PET.

Animals↗
PubMed1984

PAC studies of 111In binding to transferrin, tropolone and acetylacetone in aqueous solutions.

Time integral and time-differential PAC measurements have been made over a wide temperature range in aqueous solutions of [111In]tropolonate and [111In]acetylacetonate. The quadrupole frequency in the latter is approximately 30% higher than that in the former and the molecular volumes derived from rotational correlation times show the expected differences. Apo-transferrin was separately added to the two 111In-chelates and the transfer of activity from chelate to transferrin followed as a function of relative molar concentrations. Very much larger molar ratios of transferrin to tropolone than of transferrin to acetylacetone were required before substantial transfer of 111In from chelate to transferrin took place. This difference in affinity for transferrin could be one significant factor in explaining the enhanced ability of [111In]tropolonate to label blood cells in the presence of plasma. The determination of PAC parameters in [111In]transferrin over a range of temperatures showed that the values of quadrupole frequency obtained depended on the number of binding sites assumed. For only one 111In site per molecule, the quadrupole frequency increases by over 50% as the temperature is reduced below the freezing point of the solution. If two 111In sites are assumed there appears to be a change in the percentage occupancy of the two sites on either side of the transition.

Cycloheptanes↗