The objectives of this proposed research are: (1) to develop procedures for the boron-10 labeling of anti-CEA and anti-CSAp goat IgG which will maximize the boron-10 content without diminishing the binding activities of the antibodies; (2) to synthesize protein conjugating carborane species having an increased number of boron-10 atoms in each molecule; (3) to 3H and 14C label these molecules; (4) to determine whether boron-10 labeled anti-CEA and anti-CSAp (whole IgG and fragments) injected intravenously into tumor-bearing golden hamsters can concentrate boron-10 in the areas of the tumors; (5) to evaluate the effectsof thermal reaction irradiation of these areas. Methodology includes: (1) boron-10 labeling anti-CEA and anti-CSAp goat IgG by diazo coupling, isothiocyanate linkages and sulfonamide linkages; (2) determining the immunoglobulin immunoreactivity after boron-10 labeling by radioimmunoassasy; (3) modifying the carborane molecules to contain polar ionic water solubilizing groups and carbohydrate groups to decrease the amount of antibody precipitaion during boron-10 labeling; (4) synthesizing protein conjugating molecules containing multiple carborane cages and boron-10 enriched carboranes using 10BF3.CaF2 as the precursor; (5) synthesizing 3H and 14C labeled carborane species using tritiated water and 14C enriched phenylacetylene as precursors; (6) cleanly separating all protein conjugating carborane species using preparative high pressure liquid chromatography techniques; (7) injecting boron-10 labeled anti-CEA and anti-CSAp (whole IgG and fragments) into tumor-bearing golden hamsters and measuring the boron-10 concentration differential between tumor and adjacent normal tissue using the 3H and 14C labels; (8) irradiating with thermal neutrons the areas of the tumors and evaluating the localixed destructive nature of neutron capture therapy using boron-10 labeled tumor specific antibodies. This proposal falls within the objective of the Biological Response Modifiers Program.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA031753-07S1
Application #
3169829
Study Section
(SSS)
Project Start
1982-07-01
Project End
1990-03-31
Budget Start
1988-07-01
Budget End
1990-03-31
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095