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Biomedical subjects

G A Kirk

Publications and source records attributed to G A Kirk.

9 recordsLinked to original sources

Bifunctional antibody: a binary radiopharmaceutical delivery system for imaging colorectal carcinoma.

In clinical studies we have evaluated a unique monoclonal antibody-based drug delivery system, a bifunctional antibody designed to deliver imaging or therapeutic agents, such as radioisotopes, drugs, or biologics, to tumor cells, while minimizing the dose to normal tissue. The bifunctional antibody, with one specificity to a tumor-associated antigen (carcinoembryonic antigen) and another specificity to a hapten, is injected and allowed to localize at a tumor site for 4 days. A hapten, tagged with a radioisotope, is subsequently injected for delivery to and capture by the prelocalized antibody at the tumor site. In studies reported here, the sulfhydryl groups of Fab' fragments of ZCE-025 and CHA-255 were linked with bis-maleimidomethyl ether to form an F(ab')2 bifunctional antibody coupled by a stable thioether linkage. EOTUBE, a hydroxyethylthiourido derivative of benzyl EDTA, was used as the hapten carrier of 111In. Fourteen patients 62-82 years old with recurrent or metastatic adenocarcinoma of the colon were studied. Twenty of 21 known lesions were imaged, and eight of nine new lesions were confirmed. With this fundamentally new approach to drug delivery, clearance from normal tissue is rapid, and high tumor:normal tissue ratios are expeditiously achieved.

Adenocarcinoma

The pitfalls of technetium Tc 99m/thallium 201 parathyroid scanning.

Technetium Tc 99m/thallium 201 parathyroid scanning has been proved to be effective by multiple researchers. A review of 54 patients who underwent scanning and operations at an institution showed the scans to be accurate in 83%. There were 15% false-negative and 2% false-positive scans. The pitfalls of parathyroid scanning can be related to false-positives and false-negatives.

Adenoma

Enhancement of monoclonal antibody binding to melanoma with single dose radiation or hyperthermia.

We undertook this study to determine whether radiation (10 Gray, single dose) or water bath hyperthermia (41 degrees C, 45 min) could enhance binding of 111In-labeled anti-p97a monoclonal antibody (MAb) to human melanoma tumors transplanted subcutaneously into nude mice. Sixty animals were given injections of 1-2 X 10(7) Brown C5513 melanoma cells. At 1-2 weeks postinjection, two-thirds of the mice were treated (one-third served as controls). Within 3 hours after treatment, each animal was given iv 2 muCi 111In-anti-p97a MAb. At 24 and 48 hours thereafter, whole-body scans were done with the use of a MaxiCamera 300 A/M unit, and the ratio of activity at the tumor and liver was determined. Some animals were kept for 7 days posttreatment, whereas others were taken after the 48-hour scan for determination of biodistribution of the radiolabeled complex. Enhancement of MAb binding was demonstrated by either modality, although enhancement was more consistent with radiation. The therapeutic efficacy of MAb may be enhanced with increased binding of radioactive MAb complexes through single dose radiation or hyperthermia.

Animals

Particulate myocardial perfusion scintigraphy: its clinical usefulness in evaluation of coronary artery disease.

The determination of myocardial viability is a crucial parameter in the evaluation of a patient with coronary artery disease. Particulate myocardial perfusion scintigraphy (PMPS) is one of several methods available for this determination. A brief comparison between PMPS and two other commonly used methods is described in this review. The technique and analysis are described and applied to 194 patients with 366 surgically bypassed regions. The patients are analyzed for postoperative regional wall function and for total ventricular function as expressed by ejection fraction. PMPS is a highly accurate and unique study for clinically predicting myocardial viability.

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