BIO 300, a Nanosuspension of Genistein, Mitigates Radiation-Induced Erectile Dysfunction and Sensitizes Human Prostate Cancer Xenografts to Radiation Therapy

• DOI: 10.1016/j.ijrobp.2019.05.062
• Publication Date: 2019-06-05T01:50:37Z
• Authors: Isabel L. Jackson; Rada Pavlovic; Allen A. Alexander; Caroline Q. Connors; Diana Newman; Javed Mahmood; John Eley; Adam J. Harvey; Michael D. Kaytor; Zeljko Vujaskovic
• Keywords: Male; Penile Erection; Prostate; Mice, Nude; Blood Pressure; Radiation-Protective Agents; Drugs, Investigational; Fibrosis; Genistein; Rats; 3. Good health; Rats, Sprague-Dawley; Disease Models, Animal; Mice; Radiation Injuries, Experimental; Random Allocation; 03 medical and health sciences; 0302 clinical medicine; Erectile Dysfunction; Regional Blood Flow; Animals; Nanoparticles; Penis

To assess whether BIO 300, a synthetic genistein nanosuspension, improves the therapeutic index in prostate cancer treatment by preventing radiation-induced erectile dysfunction (ED) without reducing tumor radiosensitivity.Male Sprague-Dawley rats were exposed to 25 Gy of 220-kV prostate-confined x-rays. Animals were randomized to receive sham radiation therapy (RT), RT alone, RT with daily BIO 300 at 2 experimental dosing regimens, or RT with daily genistein. Erectile response was evaluated over time. Penile shaft tissue was harvested for histologic analyses. Murine xenograft studies using prostate cancer cell lines determined the effects of BIO 300 dosing on RT efficacy.Prostate-confined RT significantly decreased apomorphine-induced erectile response (P < .05 vs sham RT). Erection frequency in animals receiving prophylactic treatment with BIO 300 starting 3 days before RT was similar to sham controls after RT. Treatment with synthetic genistein did not mitigate loss in erectile frequency. At week 14, post-RT treatment with BIO 300 resulted in significantly higher quality of erectile function compared with both the RT arm and the RT arm receiving genistein starting 3 days before irradiation (P < .05). In hormone-sensitive and insensitive prostate tumor-bearing mice, BIO 300 administration did not negatively affect radiation-induced tumor growth delay.BIO 300 prevents radiation-induced ED, measured by erection frequency, erectile function, and erection quality, when administered 3 days before RT and continued daily for up to 14 weeks. Data also suggest that BIO 300 administered starting 2 hours after RT mitigates radiation-induced ED. Data provide strong nonclinical evidence to support clinical translation of BIO 300 for mitigation of ED while maintaining treatment response to RT.