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Biomedical subjects

A M Zimmer

Publications and source records attributed to A M Zimmer.

53 records · Page 3Linked to original sources
PubMed1987

Pharmacokinetics of 99mTc(Sn)- and 131I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments in nude mice.

The biodistribution, radioimmunoimaging, and high pressure liquid chromatography activity profiles of 99mTc(Sn) and 131I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments were compared. Nude mice, bearing specific (colon carcinoma, LS174T) and nonspecific (pancreatic carcinoma, MIA) xenografts were given injections of the respective radiolabeled antibody fragments and also of irrelevant 125I-labeled antibody fragments (MOPC-21). The animals were imaged at 24 h after being given injections, they were sacrificed, and biodistribution studies were performed. Results of the study showed high kidney uptake [48.6% injected dose (ID)/g +/- 8.1% (SD)] and low tumor uptake (1.5% ID/g +/- 0.6%) for 99mTc(Sn)-labeled fragments and higher uptake (4.4% ID/g +/- 0.6%) for 131I-labeled fragments, resulting in a higher localization index for the radioiodinated monoclonal antibody fragments. Imaging results showed good tumor visualization at 24 h after injection for the 131I-labeled fragments and poor tumor visualization with predominant kidney uptake for 99mTc(Sn)-labeled fragments. After radiolabeling, high pressure liquid chromatography analysis indicated that 131I was primarily associated with F(ab')2 fragments, whereas 99mTc was mostly associated with Fab' fragments.

Animals↗
PubMed1987

Considerations for tomographic imaging of monoclonal antibodies.

Monoclonal antibodies have begun to assume a significant role in clinical research. The ability to label these agents has initiated research in the areas of radioimmunodetection and radioimmunotherapy. In the case of antibodies directed against tumor antigens, imaging has been employed to help assess location and extent of disease, and to provide information and extent of disease, and to provide information concerning biodistribution to be used in subsequent dosimetric calculations. Because of the low counting statistics characteristic of such images, the use of single photon emission computed tomography (SPECT) is suggested as a potential method of improving the diagnostic yield from image data. Careful attention to acquisition parameters and image processing options is needed if these goals are to be achieved.

Antibodies, Monoclonal↗
PubMed1987

Radioimmunodetection and radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled monoclonal antibody: an Illinois Cancer Council Study.

A radiolabeled murine monoclonal antibody (T101) was used for imaging and therapy of six patients with cutaneous T cell lymphoma (CTCL). Radioimmunodetection was performed with a 5.6 to 13.1 mCi 131I-T101 preparation (9.6 to 10.5 mg). A therapeutic dose of 100.5 to 150.1 mCi 131I on 9.9 to 16.9 mg of antibody was administered to five patients, with subsequent retreatment following plasmapheresis in three patients at the time of disease progression. All patients responded to their initial therapy and two patients responded to retreatment. Regression of skin lesions and peripheral adenopathy was witnessed. All patients reported resolution of their chronic pruritus. The duration of response ranged from 3 weeks to 3 months. Acute toxicity included fevers, pruritus, and mild dyspnea in two instances. Myelosuppression was seen in patients receiving the 144.7 mCi, 145.0 mCi, and 150.1 mCi 131I-T101 doses. Radioimmunodiagnostic and therapy studies included gamma scintigraphy, plasma, urinary, and wholebody antibody clearances, and biodistribution determined from skin, bone marrow, and liver biopsies. Immunologic studies included immunoperoxidase staining of target tissues, immunofluorescent flow cytometric analysis on peripheral blood and bone marrow, assays for serum blocking factors, determination of a human antimouse antibody (HAMA) response, and quantitation of circulating T101 levels. These preliminary data suggest that 131I-T101 has therapeutic potential in CTCL and that myelosuppression will be the limiting toxicity.

Aged↗
PubMed1985

Radioimmunoimaging of human small cell lung carcinoma with I-131 tumor specific monoclonal antibody.

In this study, an IgM monoclonal antibody (MAb600D11) directed against human small cell lung cancer (NCI-H69) was radiolabeled with iodine-131, and the biodistribution and image quality of the radiolabeled antibody was evaluated. Radiolabeling was achieved in a solid-phase system consisting of 1,3,4,6-tetrachloro-3a,6a-diphenylglycoluril. Labeling efficiencies and protein purification were accomplished using gel exclusion chromatography while radioimmunoreactivity was determined using a solid-phase radioimmunoassay procedure. The biodistribution of I-131-labeled MAbs was determined in Sprague-Dawley rats up to 7 days after injection. Highest organ concentrations were observed in liver (3.91 +/- 0.47 (SD) and 0.17 +/- 0.04 (SD) mean percent injected dose at 1-7 days after injections) and in thyroid (5.33 +/- 0.71 (SD) and 5.32 +/- 2.01 (SD) mean percent injected dose at 1-7 days after injection). Nude mice, bearing either a small cell lung tumor (NCI-H69) or a nonspecific tumor (adenocarcinoma), were injected with 400-800 microCi of I-131 labeled monoclonal antibody. Optimum tumor visualization was observed 2-4 days after injection with tumor concentrations as high as 10.4% of the initial injected dose. The results demonstrated that radioimmunoimaging of human small cell lung carcinoma was feasible with the tumor-specific IgM I-131-labeled MAb.

Adenocarcinoma↗
PubMed1983

Leucocyte labeling with colloidal 111In in whole blood.

A simple method of 111In leucocyte labeling in whole blood is described. 111In-colloid is initially formulated using iron (50 micrograms Fe+3). 111In-colloid is then added to 10mL of whole blood and leucocyte labeling is achieved by phagocytosis. Non-phagocytosed 111In-colloid is solubilized using a sodium citrate solution. Labeling efficiencies of 60-80% have been achieved with this method. If needed, excess 111In-soluble-complexes can be removed in the plasma fraction by appropriate centrifugation. The labeling method described is easy to use and has the advantage of selectively labeling leucocytes in a whole blood mixture.

Colloids↗
PubMed1982

Rapid miniaturized chromatography for Tc-99m IDA agents: comparison with gel chromatography.

Miniaturized chromatography systems for determining free pertechnetate and hydrolyzed reduced 99mTc levels in commercial 99mTc-labeled iminodiacetate (IDA) hepatobiliary radiopharmaceuticals were evaluated and the results compared with gel chromatography column scanning (GCS). Commercial IDA agents were evaluated including 2,6-dimethyl IDA, p-isopropyl IDA, p-butyl IDA, and 2,6-diisopropyl IDA. Of all the chromatography systems evaluated, only Gelman ITLC-SA with 20% NaCl and Gelman ITLC-SG with distilled water correlated with GCS in evaluating free pertechnetate and hydrolyzed reduced 99mTc levels for all IDA radiopharmaceuticals. The miniaturized chromatography procedure, as outlined, is rapid, taking less than 4 min, and can easily be incorporated into the daily quality control program in any nuclear medicine facility.

Chromatography↗
PubMed1981

The paper spot test: a rapid method for quantitating stannous concentrations in radiopharmaceutical kits.

We have developed a simplified, semiquantitative test for the determination of stannous tin in pyrophosphate and other tin-containing radiopharmaceuticals, excluding those stabilized with ascorbic acid and MAA preparations. The test involves the formation and disappearance of a positive red color complex in the presence of Sn(II) and in acidified porphyrin solution. With this technique, the time of spot disappearance is directly proportional to the Sn(II) concentration spotted. The procedure is easy to use, requiring only a high-intensity light source (30-watt light bulb) and a timing device. The test is accurate, reproducible, and sensitive to Sn(II) levels as low as 40 micrograms/ml. Because the procedure is rapid (requiring less than 5 min), it can easily be incorporated into the routine radiopharmaceutical quality-control program of any nuclear medicine facility.

Diphosphates↗
PubMed1979

Technical parameters of in vivo red blood cell labeling with Technetium-99m.

The in vivo labeling of red blood cells (RBC) using sequential injections of stannous pyrophosphate and 99mTc-pertechnetate has resulted in excellent blood pool images since it was initiated in our laboratory in 1975. Recently certain technical parameters of the procedure have been further researched and clarified. The optimum RBC labeling has been obtained by using 1.43 mg "cold" Sn-PYP/1000 ml blood and a 30-minute lag time prior to pertechnetate injection (15-20 mCi). The binding of 99mTc to RBCs is not instantaneous, but requires several minutes for completion. The "secondary" RBC labeling effect of additional pertechnetate, added after the initial in vivo labeling, demonstrates an initial rapid fall in the labeling efficiency as a function of time followed by a more gradual decrease; the level of baseline (spontaneous) RBC labeling is achieved approximately 8 days after an initial in vivo labeling. Monitoring in vivo RBC labeling over several hours indicates that more than 90% of the initial activity was still in the vascular blood pool at 4 hours, bound to RBCs.

Erythrocytes↗
PubMed1978

Experimental investigations of the possible cause of liver appearance during bone scanning.

Rats were injected with 99mTc-Sn-diphosphonate preparation containing various concentrations of Al+3, ranging from 0 microgram/ml to 60 microgram/ml, and whole-body rat images were obtained at two hours postinjection to assess soft-tissue uptake. Uptake (kidney and liver) occurred at approximately 20 microgram/ml Al+3. [This is the maximum allowed in pertechnetate eluate by the Nuclear Regulatory Commission (NRC). ] Increased soft-tissue uptake and progressive degradation of bone scan images occurred with higher Al+3 concentrations. Chromatographic analysis confirmed the breakdown of the radiopharmaceutical preparation containing 20 microgram/ml or more Al+3. Millipore filtration showed no evidence of large colloid particles (greater than 0.2 micrometer).

Aluminum↗
PubMed1978

Rapid miniaturized chromatographic quality control procedures for iodinated radiopharmaceuticals.

A rapid, miniaturized chromatographic system was developed to determine the labeling efficiency of iodinated radio-pharmaceuticals including I-131 orthoiodohippurate, I-131 rose bengal, I-125 RISA, and I-131 19-iodocholesterol. The system consists of three specific chromatography strips (Whatman 31ET paper chromatography, silica gel and silicic acid instant thin-layer chromatography) and three solvents (chloroform:glacial acetic acid in a 1.00:0.05 v/v mixture, absolute methanol, and 0.9% sodium chloride). The strips are color-coded, miniaturized, and appropriately labeled. The chromatographic quality control procedures are easy to use, rapid, and can be incorporated easily in a routine quality control program.

Chromatography↗
PubMed1977

Rapid miniaturized chromatographic quality-control procedures for Tc-99m radiopharmaceuticals.

Our laboratory has adopted a complete miniaturized charomatography system for Tc-99m radiopharmaceuticals in order to improve upon the commercial systems currently available. Three distinct, separate, chromatographic procedures are used to determine the labeling efficiencies of Tc-99m-labeled sulfur colloid, MAA, stannous chloride, phytate, DMSA, DTPA, pyrophosphate, diphosphonate, methylene diphosphonate, polyphosphate, and glucoheptonate. The chromatographic systems include Whatman 31 ET paper and acetone, Gelman ITLC-SG and 0.9% sodium chloride, and Gelman ITLC-SA and acetone. The chromatographic strips are miniaturized (1 X 6 cm), colored-coded, marked, and numbered. All the chromatographic quality-control procedures are simple, rapid, and can easily be incorporated into the routine quality-control program of any nuclear medicine facility.

Chromatography↗
PubMed1977

In vitro technetium-99m red blood cell labeling using commercial stannous pyrophosphate.

A simple and rapid technique of preparing technetium-99m-labeled erythrocytes using commercial stannous pyrophosphate as the reducing agent was developed. The technique involves incubating red cells with stannous pyrophosphate, centrifugation, and addition of Tc-99m pertechnetate to the red cell fraction. A mean red cell labeling efficiency of 94% was achieved in 10 patient samples and less than 5% in vitro dissolution of Tc-99m red blood cells occurred up to two hours after preparation.

Drug Stability↗
PubMed1976

Assay of 32P-sodium phosphate using a commercial dose calibrator.

Dose calibrators are not usually used to measure the activity of pure beta-emitting radionuclides. In this work, the activity of 32P-sodium phosphate was accurately measured with a Capintec CRC-2 dose calibrator. Using a calibration knob setting of 012 on the 1-mCi range, the 32P dose (in mCi) could be calculated directly simply by multiplying the instrument readout by 10. The dose calibrator response was found to be linear at this knob setting and moderate alterations in geometry produced no significant changes.

Phosphorus Radioisotopes↗
PubMed1975

A precise chromatography system for specific technetium-99m radiopharmaceuticals.

New chromatographic procedures are needed to accurately determine the radiochemical purity of technetium-99m labeled radiopharmaceuticals. A chromatography system has been developed for technetium-99m diethylenetriaminepentacetic acid, technetium-99m diphosphonate, and technetium-99m pyrophosphate. The technique involves spotting the radiopharmaceuticals on instant thin layer chromatography-silica gel and developing with acetone (solvent from migrates approximately 12 cm from the origin), air drying, and redeveloping the strip in normal saline (solvent front migrates approximately 6 cm from the origin). The procedure is simple to perform, rapid, accurate, and clearly separates technetium-99m pertechnetate, the technetium-99m radiopharmaceutical, and hydrolyzed reduced technetium-99m. It can be applied in most nuclear medicine laboratories and has the potential to predict the quality of radionuclide images obtained.

Chromatography, Thin Layer↗
PubMed1975

Enzymatic inhibition of diphosphonate: a proposed mechanism of tissue uptake.

Enzymes have been proposed as tissue receptors that bine 99mTc-stannous diphosphonate and its analogs. Incubation of diphosphonate with several enzymes demonstrated inhibition of acid and alkaline phosphatase activity but showed no effect on glutamic oxalacetic transaminase and lactate dehydrogenase activity. Complete reversal of the diphosphonate-induced inhibition of alkaline phosphatase activity occurred when calcium ion was added to the reaction. The specificity of calcium to induce reversal was dispelled when magnesium ion gave identical results. Diphosphonate-induced inhibition of acid phosphatase, however, was not reversed by calcium or magnesium.

Acid Phosphatase↗
PubMedDate not supplied

Hepatobiliary delivery of polyaminopolycarboxylate chelates: synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate.

A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance.

Animals↗