NEW BORON CONTAINING AMINO ACIDS AND PEPTIDES FOR BORON NEUTRON CAPTURE THERAPY

BORON NEUTRON CAPTURE THERAPY (BNCT) HAS A CLEAR THEORETICALADVANTAGE OVER OTHER TECHNIQUES AS A METHOD OF DELIVERING CELL-KILLING RADIATION TO TUMORS. NEW BORON COMPOUNDS ARE NEEDED WHICH CAN SELECTIVELY LOCALIZE IN TUMORS AND UPON CAPTURE OF THERMAL OR EPITHERMAL NEUTRONS, PRODUCE RADIATION WHICH KILLS TUMOR CELLS BUT SPARES NORMAL TISSUE AND BLOOD. THE PHASE I EFFORT STARTS WITH THE PREMISE THAT BORON ANALOGUES OF AROMATIC AMINO ACIDS AND PEPTIDES CONTAINING ONE OR MORE BORONATED AROMATIC AMINO ACID ANALOGUES MAY SHOWCONCENTRATION AND RETENTION IN TUMOR CELLS AND BE SUITABLE FOR BNCT. A SIGNIFICANT RELATIVE BIOLOGICAL EFFECT (WASHED CELLS) WAS INDICATED IN A PRELIMINARY (NEUTRON CAPTURE) BIOLOGICAL EFFICACY STUDY IN CELL CULTURE USING A (GLYCINE) BORON AMINO ACID - AROMATIC AMINO ACID DIPEPTIDE. THE PHASE I EFFORT SHOULD RESULT IN A NUMBER OF NEW BORON ANALOGUES OF AROMATIC AMINO ACIDS AND SELECT PEPTIDE DERIVATIVES. THE NEWLY PREPARED COMPOUNDS ARE EXPECTED TO POSSESS (AND WILL BE SCREENED FOR) ANTINEOPLASTIC (AND OTHERPHARMACOLOGICAL ACTIVITY) AS HAS BEEN FOUND FOR THE RELATED SIMPLER GLYCINE SPECIES. BIOLOGICAL EFFICACY STUDIES FOR BNCT WILL ALSO BE CARRIED OUT. THUS, NEW THERAPEUTIC AGENTSFOR THE TREATMENT OF CANCER ARE POSSIBLE WHICH HAVE A COMBINED CELL-KILLING EFFECT (ON CANCEROUS TISSUE) BY CHEMOTHERAPY AND BNCT.