New methods for localizing infection: a role for avidin-biotin?
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Animals↗
Biomedical subjects
D A Goodwin
Publications and source records attributed to D A Goodwin.
Pretargeted immunoscintigraphy: effect of hapten valency on murine tumor uptake.
A method of radioimmunoscintigraphy using bivalent "Janus" haptens with an apparent enhanced affinity ("avidity") for the antibody is described. Janus with 50 micrograms pretargeted Mab WC3A11 resulted in significantly higher murine tumor concentrations (approximately 7%/g) compared to monovalent haptens (approximately 1.4%/g, p < 0.001), and the same high tumor-to-background ratios (approximately 3/1). Janus was synthesized by coupling two molecules of BABE together with a 1,4 butanedithiol linker. Janus itself was rapidly excreted (T1/2b = 42 min) by the kidneys and did not concentrate in any other organs or tissues. Three-step pretargeted immunoscintigraphy (binder, chaser, tracer) with 111In- or 67Ga-Co(III) Janus produced excellent mouse tumor images in 3 hr with high tumor-to-background ratios. The use of short-lived tracers, such as 99mTc and 68Ga, with a T1/2p of hours to image antibodies that localize slowly over several days in vivo is accessible with this new technology.
Animals↗
Tumor imaging with indium-labeled biotin.
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Antibodies, Monoclonal↗
The in vivo distribution of human peripheral blood lymphocytes and lymphokine-activated killer cells adoptively transferred in human pancreatic cancer-bearing nude mice.
In this study we evaluated human pancreatic cancer xenotransplanted into nude mice as a model suitable for adoptive immunotherapy studies. A pancreatic cancer cell line (MIA PaCa-2) was chosen and its growth in nude mice and sensitivity to lysis by human lymphokine-activated killer (LAK) cells were characterized. This line grew in 96% of the cases when young (4- to 6-week-old) Swiss/NIH nude mice were used. The line was highly sensitive to lysis by LAK cells in a standard chromium-51 release assay (67.8%), similarly to other cell lines known to be highly sensitive, such as K562 (75.6%) and the melanoma cell line SU.102 (53.1%). To assess their in vivo distribution, human peripheral blood lymphocytes (PBLs) and LAK cells were adoptively transferred into nude mice after labeling with indium-111 oxine. The results of this study show that adoptively transferred PBLs and LAK cells localize in this heterologous system as they do in autologous systems. PBLs are taken up mostly by the liver and spleen. The percentage of the administered dose of radioactivity taken up corrected by weight (percent dose per gram tissue) is 64.3 +/- 15.6%d/gm (liver) and 43.5 +/- 9.5%d/gm (spleen). LAK cells are taken up by liver (43.2 +/- 5.3%d/gm) and spleen (28.0 +/- 4.9%d/gm) but also localize significantly more than PBLs in other organs such as lungs (12.9 +/- 3.5%d/gm vs 1.4 +/- 0.3%d/gm, p less than 0.01), kidneys (19.1 +/- 2.1%d/gm vs 6.3 +/- 1.5%d/gm, p less than 0.001), and pancreatic tumors growing in orthotopic position (1.93 +/- 0.36%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.05). When the nude mice are pretreated with human recombinant tumor necrosis factor, localization of LAK cells compared with PBLs is even further enhanced both in tumors implanted in the pancreas (3.1 +/- 0.5%d/gm vs 0.56 +/- 0.06%d/gm, p less than 0.01) and in the subcutis (12.5 +/- 8.3%d/gm vs 0.95 +/- 0.29%d/gm, p less than 0.001).
Animals↗
Indium-111-labeled leukocyte imaging in acute pancreatitis with suspected complicating abscess.
Indium-111-labeled leukocyte imaging is described in two cases of acute pancreatitis. The study correctly anticipated the absence in one case, and the presence in the other, of complicating abscesses.
Abscess↗
BLEDTA: tumor localization by a bleomycin analogue containing a metal-chelating group.
Two different Co(III) complexes of the antitumor antibiotic bleomycin have been prepared, and their in vivo distribution in mice has been investigated. The more thermodynamically stable of the Co(III)-bleomycin complexes has been modified by reaction with the bifunctional chelating agent 1-(p-bromoacetamidophenyl)ethylenedinitrilotetraacetic acid, to give a bleomycin derivative (BLEDTA) containing a powerful metal-chelating group. BLEDTA was radiolabeled with 111In(III) and its in vivo distribution in mice was examined. The potential of 111In-labeled BLEDTA as a tumor-visualizing agent was also investigated in humans with biopsy-proven cancers, predominantly (70%) squamous carcinoma of the head and neck. All of the 29 patients studied had at least one clinically proven site of the disease visualized with 111In-BLEDTA. These clinical results are significantly better than results we obtained in a comparable group of patients using directly labeled 111In-bleomycin and are similar to those reported by Nouel for 57Co-bleomycin [GANN Monogr. Cancer Res., 19, 301 (1976)].
Adult↗
The attachment of metal-chelating groups to protein: tagging of albumin by diazonium coupling and use of the products as radiopharmaceuticals.
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Albuminuria↗
A review of carotid cavernous fistula including diagnosis and evaluation by nuclear medicine angiography.
The various causes and differential diagnosis of carotid cavernous fistula are discussed as well as the description of the use of radionuclide angiography in the diagnosis and evaluation of patients with carotid cavernous fistulas. Radionuclide angiography has proven extremely useful in the diagnosis and follow-up of patients with carotid cavernous fistulas. The procedure is of maximum benefit in situations where repeat studies are required at frequent intervals. Five cases are described in which the nuclear medicine technique was instrumental in primary diagnosis and follow-up.
Adult↗
The use of indium-111-labeled leukocytes for abscess detection.
A case is reported in which a labeled white cell scan was helpful in the diagnosis of a periappendiceal abscess. The method of labeling is described and the usefulness of the technique discussed.
Abscess↗
Cell labeling with oxine chelates of radioactive metal ions: techniques and clinical implications.
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Abscess↗
Indium-111-labeled autologous platelets for location of vascular thrombi in humans.
Twenty-two patients suspected of having either venous or arterial thrombi were studied with In-111-labeled autologous platelets. Whole-body scans were performed 3, 24, and 48 hr following i.v. injection. Twelve patients studied with saline-washed platelets had unsatisfactory 15-min recovery and biologic half-time. When the labeling was carried out in plasma, these values compared favorably with normal values reported for Cr-51-labeled autologous platelets. Of ten patients studied using platelets labeled in plasma, three had normal scans, six had abnormal scans, and one had an equivocal scan. All six abnormal scans were confirmed with corresponding positive findings in either the venogram, arteriogram, or lung scan. J Nucl Med 19: 626-634, 1978.
Adult↗
Radiolabeled antitumor agents.
Bleomycin serves as a useful prototype for a study of the various properties required in a radiopharmaceutical for tumor imaging. Both in vitro and in vivo results using bleomycin labeled with a large number of different radionuclides have now been reported. In general, it has not been possible to predict in vivo biologic behavior solely from in vitro data. For example, 57Co-bleomycin and 111In-bleomycin both have identical patterns in several different chromatographic systems and do not break down with prolonged storage in saline, exposure to heat, or other cations. However, when the labeled bleomycin is exposed to serum transferrin (and to other as yet unidentified ligands in the body) a difference in stability becomes obvious. The stability and biologic activity of 57Co-bleomycin in humans demonstrate the validity of metal chelation as a labeling technique for this specific molecule, and also suggests that other stable chelates will have useful applications. Although 57Co-bleomycin has the most desirable biologic characteristics of all the chelates of bleomycin, the extremely long physical half-life of 57Co of 270 days creates a significant contamination problem in the hospital. Because of this, the use of 57Co-bleomycin is limited to a few specialized centers. All users have emphasized the need for a better radionuclide to produce a labeled bleomycin with the same or superior biologic characteristics to 57Co-bleomycin. Unfortunately, the elements forming the most stable chelates with bleomycin (copper, zinc, cobalt, and nickel) do not have radionuclides with suitable physical characteristics for scanning. Copper-67 may become available in the future from high-energy linear accelerators. However, even if it were available, copper will probably not have as good chemical properties as cobalt.
Abdominal Neoplasms↗
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↗
Pulmonary distribution of an inhaled radioaerosol in obstructive pulmonary disease.
Pulmonary distribution of an inhaled radioaerosol was analyzed in 20 cases of chronic obstructive pulmonary disease (COPD) and 8 of other OPD. Nonciliary/ciliary partition of the distribution correlated with the severity of airway obstruction and approximated 3:1 in mild and 1:3 in very severe obstruction. In nuclear images, the distribution featured contrast abnormalities of hyperdeposition and hypodeposition. Intense hyperdeposition most commonly occurred in hilar and perihilar large airways. In isolated instances, hyperdeposition almost certainly occurred focally at sites of partial bronchial obstruction and diffusely by expiratory trapping; hypodeposition occurred distally to bronchial obstruction and in areas of parenchymal loss.
Adult↗
Bifunctional chelates for radio-pharmaceutical labeling.
The use of the first of a new class of chelating agents for the binding of metal ions to macromolecules as a novel approach to radiopharmaceutical labeling is described. Advantages are mild reaction conditions, large variety of accessible radionuclides and reactive groups, and separation of synthetic organic chemistry from radiochemistry. Human serum albumin and bovine fibrinogen labeled with 111Indium using this technique were relatively stable in vitro and in vivo, showed little alteration in function, and have potential as tumor localizing agents in humans.
Animals↗
A study of o-cresolphthalexon and its analogs as cholescintigraphic 111In carriers.
111In has been complexed to a series of metal-complexing phthaleins and sulfonphthaleins, and the hepatobiliary excretion of the compounds were compared in rats. The highest biliary excretion was obtained with 111In-o-cresolphthalexon. In a normal human subject, sequential imaging with 111In-o-cresolphthalexon visualized his gallbladder, common bile duct, and the bowel from jejunum to rectum. The potential utility and limitation of this biliary scanning agent is discussed.
Adult↗