Antigen-Independent Methods to Improve Radioimmunotherapy of Prostate Cancer

摘要

These studies were designed to improve the outcome of radioimmunotherapy (RIT) in prostate adenocarcinoma by the inclusion of vasoactive peptides in the RIT protocol. To date three peptides able to modify vascular permeability (VP) were tested. Cytotoxicity studies indicated dose- dependent changes in cell metabolic activities after treatment with two agonists interacting with CD88 (C5aAP peptides); whereas one peptide interactive with a formyl peptide receptor-like I did not seem to have any effect on the growth of these cells in vitro. In vivo results confirmed that at least two of these peptides significantly augmented RIT with 131ICC49. The principal reason for improvements was identified as the increased tumor uptake of the radiotracer. However, there is also an indication that the generation of reactive oxygen species play a significant role. The effect of the C5aAP peptide N2's effect on VP and tumor uptake is virtually identical to the effects of the N1 peptide. The N2, however, considerably reduces the radiosensitivity of LNCaP, PC3 and DU145 cells in vitro. The in vivo studies of N2 with and without thiol group modification are in progress.