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.
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