Conference Coverage

Bombesin Research: The Prostate Cancer Connection

Bernskoetter NE, Bernedzen AF, Rold TL, Hoffman TJ

Abstract 29: 2015 AVAHO Meeting


 

References

Background: Current VA statistics estimate that as of September 2014, there were 14.9 million veterans aged ≥ 50 years. Of this population, American Cancer Society statistics predict that nearly 2.2 million male veterans will be diagnosed with prostate cancer and that more than 392,000 of these men will eventually succumb to metastatic prostate cancer. This presentation summarizes our translational research program focused on the development of theranostic radiopharmaceuticals to identify, diagnose, and treat bombesin receptor-positive (BB2r) prostate cancer. Multiple national and international research groups, including our own, have demonstrated that the BB2r is potentially an attractive prostate cancer-specific protein receptor for developing novel BB2r targeting vectors for use as diagnostic biomarkers and delivery of tumor cell specific radiotherapy. With the advances in the field to date, 3 generations of BB2r targeting vectors have been developed and undergone various levels of in vitro and in vivo evaluation, up to and includ-ing phase 1 human imaging/therapy trials. We are now currently in what we term as the t generation of BB2r-based drug production. In our first generation, BB2r-agonist constructs were developed and radiolabeled with technetium-99m and rhenium-188 for single-photon emission computed tomography imaging applications and prostate cancer cell targeted radiotherapy; the second-generation BB2r constructs incorporated indium-111, lutetium-177, and yttrium-90 into DOTA-chelated BB2r agonists; and the third-generation BB2r constructs currently under development employ indium-111, gallium-68, and lutetium-177 DOTA-chelated BB2r antagonists. Our studies in human prostate cancer xenograft models have demonstrated receptor-specific targeting of localized and disseminated disease along with significant tumor growth inhibition and improvement in overall survival when therapeutic radiolabeled constructs are used alone or in combination with chemotherapy. Future studies underway are evaluating internal organ radiation dosimetry estimates and validating the utility of concurrent BB2r imaging biomarkers to guide therapy endpoints.

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