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A D Nunn

Publications and source records attributed to A D Nunn.

At least 19 recordsLinked to original sources
PubMed1992

Direct analysis of whole blood by internal surface reversed-phase chromatography: an examination of the binding and metabolism of technetium dioxime complexes.

We have developed a method using internal surface reversed-phase (ISRP) packing for rapid on-line separation of small hydrophobic compounds from cellular whole blood components. This is achieved by the use of 75-microns ISRP chromatographic material packed into a small high-performance liquid chromatographic (HPLC) column, in conjunction with column switching. We have applied this analytical method to study the in vitro metabolism of 99mTc-BATO (boronic acid adducts of technetium dioxime) cerebral and myocardial perfusion tracers in whole blood. The results from the ISRP procedure were compared with a conventional centrifugation method of analysis. This novel HPLC methods provides a rapid, convenient and reliable method for the analysis of radioactive and non-radioactive lipophilic components in whole blood.

Animals↗
PubMed1992

Myocardial extraction of teboroxime: effects of teboroxime interaction with blood.

The isolated perfused rat heart preparation was used to determine whether the interaction of blood with either 99mTc-teboroxime, 99mTc-sestamibi or 201TI affects the extraction of these myocardial perfusion agents. Hearts were retrogradely perfused at 72 cm H2O with Krebs-Henseleit buffer equilibrated with O2:CO2 (95:5). The hearts were paced at 5 Hz. Single-pass extraction of 99mTc-teboroxime (96% +/- 1%) was greater than that of 99mTc-sestamibi (15% +/- 1%) or 201TI (30% +/- 5%). Extraction of the hydroxide form of 99mTc-teboroxime was only 43% +/- 4%. When arterial blood obtained from rats administered 99mTc-teboroxime was injected into the perfused heart, extraction of 99mTc-teboroxime decreased progressively as its time in circulation was lengthened. Similar experiments using either 99mTc-sestamibi or 201TI showed that extraction of these agents was neither affected by the presence of blood nor residence in circulation. For 99mTc-teboroxime, extraction was 99.5% +/- 0.5%, 57% +/- 13%, 20% +/- 2% at 1, 5, and 60 min postinjection, respectively. In separate experiments, HPLC analysis of blood at 5, 15 and 60 min postinjection indicated that only 34% +/- 4%, 13% +/- 2%, and 2% +/- 1%, respectively, of the total 99mTc-teboroxime was free and was associated with extraction values of 44% +/- 7%, 28% +/- 5%, and 19% +/- 3%, respectively. The percentage of this free radioactivity that converted from the chloro to the hydroxide form was 9% +/- 2%, 6% +/- 2%, and 2% +/- 1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Measurement of myocardial blood flow using a co-injection technique for technetium-99m-teboroxime, technetium-96-sestamibi and thallium-201.

We have compared apparent myocardial blood flow (MBFapparent) indicated by 99mTc-teboroxime, 96Tc-sestamibi and 201TI to true MBF indicated by radiolabeled microscopheres using a technique for the co-injection of four radionuclides in the same animal. Studies were performed using rats in a single-pass model to obtain global MBF and using dogs in a multiple-pass model to determine regional MBF. To provide a wide range of MBF, adenosine was administered intravenously and the left anterior descending coronary artery was then ligated in the dogs, or hypercapnia was induced by decreasing respiratory frequency in the rats. The microsphere formula for determining MBF was applied to all agents. When MBFapparent was plotted as a function of true MBF, the ability of each agent to measure changes in true MBF was demonstrated by the proximity of the plotted function to the line of identity. For both the single and multiple-pass studies, statistical analysis of the nonlinear relationship between MBFapparent and true MBF showed that 201TI and 99mTc-teboroxime approximate true MBF better than 96Tc-sestamibi (p less than 0.001) under the conditions used in the present studies. In the single-pass studies, 99mTc-teboroxime approximated true MBF better than 201Tl (p less than 0.05), but in the multiple-pass experiments, 201Tl approximated true MBF better than 99mTc-teboroxime in only one dog (p less than 0.01) with no difference in the other two. Determination of the permeability-surface area product, PS, for each agent shows that the higher fidelity to true MBF obtained with 201Tl and 99mTc-teboroxime is related to substantially greater PS values for these agents relative to 96Tc-sestamibi.

Animals↗
PubMed1992

Absorbed radiation dose to humans from technetium-99m-teboroxime.

Tissue distribution data obtained in nine normal volunteers were used to estimate the radiation dose to humans after intravenous administration of 99mTc-teboroxime (Cardiotec). Organ uptake as percent of injected dose was measured using quantitative SPECT. Non-linear regression analysis was performed on the organ time-activity data using SYSTAT software. Cumulative activities in these organs were determined by calculating the area under the respective curves after accounting for the physical decay of the radionuclide. The absorbed dose to individual organs was estimated using the MIRDOSE 2 program. The gallbladder and the upper large intestine (ULI) are the target organs and will receive respectively 26.5 and 33.2 muGy/MBq (98 and 123 mrad/mCi) 99mTc-teboroxime under the assumption that the gallbladder empties every 6 hr. The dose to the gallbladder decreases at shorter emptying intervals; with intervals of 3, 4, and 5 hr, the respective doses to the gallbladder are 18.2, 21.0 and 23.7 muGy/MBq (67.4, 77.8, and 87.9 mrad/mCi) 99mTc-teboroxime. However, the dose to ULI remains almost constant at 123 mrad/mCi and will be the limiting factor.

Gallbladder↗
PubMed1991

Chloro----hydroxy substitution on technetium BATO [TcCl(dioxime)3 BR] complexes.

The neutral, seven coordinate complexes of technetium known as the BATO (Boronic acid Adducts of Technetium diOximes) complexes have shown their utility as myocardial and cerebral perfusion agents. The axial chloride ligand of the BATO complexes [99mTcCl(dioxime)3 BR] is labile to substitution by a competitive anion; under physiological conditions, the axial chloride ligand can be replaced by a hydroxy group. The chloro and hydroxy analogs have different biodistributions and single-pass cerebral extraction efficiencies. The influence of structure on the rate of the in vitro chloro/hydroxy exchange process has been studied. The mechanism of axial ligand exchange was found to be SN1-CB, which proceeds by way of a transient, neutral six coordinate complex. Evidence is presented which indicates that chloro/hydroxy exchange is not the mechanism by which BATO complexes are retained in the brain.

Animals↗
PubMed1990

Radiopharmaceuticals for imaging myocardial perfusion.

A replacement for 201Tl used in myocardial perfusion imaging with a 99mTc-labeled complex is a long-sought goal. Now, at least three varieties of 99mTc-complexes are being made available for clinical studies. This review summarizes the development of these agents and presents basic research data accumulated in this area. Also, relevant clinical radiopharmaceutical protocols and relative merits of competing 99mTc-agents are discussed.

Animals↗
PubMed1990

A neutral lipophilic technetium-99m complex for regional cerebral blood flow imaging.

Technetium-99m-DMG-2MP (Chloro[bis[2,3-butanedionedioxime(1-)-0][2,3- butanedionedioximato (2-)-N,N',N'',N''',N'''',N'''''] (2-methylpropyl borato (2-))technetium]), also known as SQ 32097 is a member of a family of neutral lipophilic compounds generally known as boronic acid adducts of technetium dioxime complexes (BATOs). After i.v. administration, the concentration of [99mTc]DMG-2MP in various regions of the brain appears to be proportional to blood flow. In rats, 1.1% ID was in the brain at 5 min postinjection when the blood contained less than 3% ID. Over 24 hr excretion was 59% in the feces and 23% in the urine. The activity in monkey brain at 5 min was 2.8% ID and it cleared with a t1/2 of 86 min. Autoradiographs of monkey brain sections showed excellent regional detail with a gray/white ratio of 3.6 at 10 min. The distribution of [99mTc]DMG-2MP in the monkey brain corresponds to the known cytoarchitectural pattern of cerebral glucose metabolism. The properties of [99mTc]DMG-2MP make it a potentially useful agent for cerebral perfusion imaging in man.

Animals↗
PubMed1976

Covalent attachment of metal chelates to proteins:the stability in vivo and in vitro of the conjugate of albumin with a chelate of 111indium.

Human serum albumin has been conjugated to 1-(p-bnezenediazonium)-(ethylenedinitrilo)tetraacetic acid, a powerful chelating agent, and radioactive 111indium ions have been added specifically to the chelating groups. The product, with a specific radioactivity of about 1 mCi/mg of protein, was employed as a radiotracer in scintillation scanning studies with human volunteers. Results show that 48 hr after injection, practically all of the label remains attached to albumin. This is confirmed by electrophoresis of serum proteins; 7 days after injection, 85% of the radioactivity in the serum is still in the albumin fraction. These observations agree with in vitro studies of the labeled albumin in human serum, where loss of the metal ion from the chelating group to the protein transferrin amounts to less than 3% after 1 week and less than 5% after 2 weeks. Measurements of the distribution of label in mice up to 23 days after injection suggest that metabolism of the labeled protein does not lead to binding of indium ions by transferrin. The binding of indium and other metal ions by transferrin has previously posed a major impediment to the use of metal chelates for in vivo diagnostic procedures. Demonstration of the kinetic inertness of the chelate in these experiments suggests the use of related chelates as physical probes of biological systems.

Animals↗
PubMed1976

Interactions between bleomycins and metals.

Gel filtration has shown that there are considerable differences between the metal complexes of bleomycin A2 and B2 with indium, cobalt or copper. Differences in the rates of formation of the complexes have also been found and it is thought that these effects are due to a difference in co-ordination between the metals and the bleomycin. The co-ordination changes are thought to be the cause of the differences in in vivo distribution of metal bleomycin complexes found in the radiodiagnosis of tumours. The ease of formation of the copper or cobalt complexes is suggested as a possible mechanism for the inhibition of the attack of DNA by bleomycins.

Bleomycin↗
PubMedDate not supplied

Technetium labeling of monoclonal antibodies with functionalized BATOs. 1. TcCl(DMG)3PITC.

BATO (boronic acid adduct of technetium dioximes) complexes, TcCl(dioxime)3BR, were prepared in which the boron substituent (R) was the protein-reactive m-phenyl isothiocyanate (PITC). The 99TcCl(dioxime)3PITC complexes [dioxime = dimethylglyoxime (DMG) or cyclohexanedione dioxime (CDO)] were prepared from 99Tc(dioxime)3(mu-OH)SnCl3 and characterized. The X-ray crystal structure of 99TcCl(DMG)3PITC was determined. The 99mTc complexes were prepared from 99mTcO4- in a process using a freeze-dried kit, either in a one-step procedure or via 99mTcCl(dioxime)3. Initial labeling studies with 99mTcCl(dioxime)3PITC were performed on glycine and polylysine and, subsequently, on mouse IgG and the B72.3 monoclonal antibody. Covalent attachment of 99mTcCl(DMG)3PITC to B72.3 was demonstrated by SDS-PAGE electrophoresis. B72.3 labeled with 99mTcCl(DMG)3PITC displayed high binding to a TAG 72 affinity column and had a distribution in normal mice similar to that reported for iodine-labeled B72.3.

Animals↗
PubMedDate not supplied

Technetium labeling of monoclonal antibodies with functionalized BATOs: 2. TcCl(DMG)3CPITC labeling of B72.3 and NP-4 whole antibodies and NP-4 F(ab')2.

BATO (boronic acid adduct of technetium dioximes) complexes, TcCl(dioxime)3BR, were prepared in which the boron substituent (R) was the protein-reactive 2-carboxy-4-phenyl isothiocyanate (CPITC). The 99Tc complexes, where the dioxime was either dimethylglyoxime (DMG) or cyclohexanedione dioxime (CDO), were prepared and characterized. The 99mTc complex TcCl(DMG)3CPITC was prepared from a freeze-dried kit and used to label B72.3 (anti-TAG.72) and NP-4 (anti-CEA) whole antibodies, and the NP-4 F(ab')2 fragment. SDS-PAGE electrophoresis indicated that the labeling reagent was strongly bound to antibody. The labeled antibodies displayed high binding to affinity columns and good tumor uptake in GW39 tumor-bearing mice.

Animals↗