The utilization of in vitro radiolabeled white cells has become a useful means to locate sites of abscess or infection in patients with advantages over CT and ultrasound. The objective of this project is to develop a quick and efficient in vivo cell labeling method to replace the current in vitro 111-In oxine and 111-In tropolone white cell labeling procedure used as a diagnostic tool in Nuclear Medicine today. The proposed project will explore the monoclonal antibody as a vehicle by which to radiolabel T-helper cells in vitro and in vivo by using a novel technique of an avidin linked monoclonal antibody and a subsequent 111-In-biotin as the radiotracer. This technique takes advantage of the specificity of monoclonal antibodies for a distinct cell population and the strong association constant of avidin for biotin; i.e., (10 15M). The antibody chosen for this study is an anti T-helper cell monoclonal antibody. The direction of the project is to couple the antibody to avidin or streptavidin. The antibody-avidin complex will be injected, allowed to localize at specific sites and the excess to clear the system. At an experimentally determined time, 111-In- DTPA-biotin will be injected. The already localized antibody- avidin will be radiolabeled via the 111-In-biotin tracer, by means of the strong biotin-avidin association. The quick clearance rate of this small radiolabeled probe: 111-In-DTPA-biotin, may allow diagnostic images to be taken within hours. Recent work of Danpure (1) has probed the use of an iodinated anti- leukocyte and anti-granulocyte monoclonal antibody. They have been successful in radiolabeling cells in vivo, however, drawbacks still remain with nonspecific binding, clearance and target to nontarget ratios via this approach. The proposed means of following the unlabeled monoclonal antibody-avidin at a tested time with a small radiotracer: 111-In-biotin should circumvent some of these problems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI025570-03
Application #
3454484
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1988-09-30
Project End
1993-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
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Hnatowich, D J; Virzi, F; Fogarasi, M et al. (1994) Can a cysteine challenge assay predict the in vivo behavior of 99mTc-labeled antibodies? Nucl Med Biol 21:1035-44
Hnatowich, D J; Fritz, B; Virzi, F et al. (1993) Improved tumor localization with (strept)avidin and labeled biotin as a substitute for antibody. Nucl Med Biol 20:189-95
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