Targeting the bombesin subtype 2 receptor for the diagnosis and treatment of metastatic prostate cancer

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] In the United States, prostate cancer is the most commonly diagnosed cancer and the third leading cause of cancer related deaths in men. With early detection, definitive therapeutic options can provide a cure. However, undetected extracapsular or regional lymph node metastasis plagues the long-term survival statistics of definitive therapies. In advanced prostate cancer, initial androgen depravation therapy has failed to control cancer progression, and regional lymph node and distant osseous metastasis are common. With metastatic spread, prostate cancer remains incurable. Aberrant expression of the bombesin subtype 2 receptor (BB2r) is present on over 80% of human prostate cancer tissues evaluated. The BB2r binds with high affinity to the bombesin peptide (BBN), stimulating agonist mediated receptor-peptide internalization into the cancer cell. Accordingly, targeting the BB2r with radioisotopes conjugated to BBN represents a promising method for diagnostic and therapeutic radiopharmaceutical development for metastatic prostate cancer. The results of this research demonstrate the potential diagnostic capabilities of BB2r targeted compounds. We also demonstrate a potential mechanism of therapeutic effect while optimizing administration timing, and evaluate the therapeutic potential of BB2r targeted radiotherapy administered with FDA approved, radiosensitizing chemotherapeutics for the treatment of metastatic prostate cancer. Taken together, BB2r targeted radiopharmaceuticals have the potential to fill a well known clinical need for the diagnosis and treatment of metastatic prostate cancer in human patients.