Abstract 2855: Monitoring tumor growth and oxygen distribution of prostate cancer xenografts in vivo using ultrasound and photoacoustic imaging
Authors: Hu Qiuhua , Ratther Ellca , Sweeney Katrina , Russell Pamela J. , Nelson Colleen C. , Tse Brian W. , Williams Elizabeth D. , Hollier Brett G. 
Published: July 2017

Introduction

Prostate cancer (PCa) is the second leading cause of cancer-related death in men. Initially, PCa growth and progression is primarily driven by androgen stimulation of the androgen receptor (AR). As such, the standard treatments for PCa target the androgen/AR axis and are collectively termed androgen targeted therapies (ATTs). In spite of initial tumor regression, tumor cells ultimately adapt and become resistant to ATTs and progress to castration resistant PCa (CRPC) or metastatic CRPC. The tumor microenvironment (TME) has long been recognized to modulate the response of tumors to therapies, however, the impact of ATTs on the TME and their contribution to the development of resistance has not been investigated. This project aims to evaluate the potential of non-invasive photoacoustic imaging combined with ultrasound imaging to assess the alterations of the TME in response to ATTs in vivo.

Methods

PCa cell lines, PC-3 (androgen-independent) and LNCaP (androgen-sensitive), were subcutaneously implanted into male severe combined immune deficiency mice. When the tumor size reached 200-300 mm3, mice were castrated and subsequently treated with enzalutamide once serum PSA had reached pre-castration levels. Ultrasound and photoacoustic (US-PA) scanning (Vevo LAZR) was performed at intervals during PCa progression to simultaneously assess changes in tumor growth, anatomical structure, vasculature, and intratumoral oxygen saturation.

Results

We provide evidence that US-PA imaging is a feasible approach to monitor TME and the response of subcutaneous prostate tumors to ATTs in vivo. PC-3 tumors (nPC-3=11) showed no response to castration in volume, but slight changes in total hemoglobin and oxygen saturation. Growth of LNCaP tumors and their subsequent responses to castration were variable (nLNCaP=10). We identified a strong correlation between ultrasound and caliper-derived tumor volumes in these models and in the majority of tumors the tumor center was more hypoxic than the peripheral tumor area, which is likely due to low oxygen and nutrient transmission and/or cell apoptosis. However, in a subset of tumors higher oxygen levels were observed in the center compared with regions nearer to the skin surface, a pattern associated with a higher rate of tumor growth compared to the rest of the cohort. Importantly, we were able to detect a relatively increase in oxygen levels between pre- and post-castration tumors in individual mice.

Conclusion

We have successfully used a non-invasive imaging method to simultaneously assess multiple biological parameters in PCa xenografts in vivo. The information gained in this study will provide a broader view of the prostate tumor response to ATTs, which has the potential to reveal novel mechanisms of therapy resistance.

Citation Format: Qiuhua Hu, Ellca Ratther, Katrina Sweeney, Pamela J. Russell, Colleen C. Nelson, Brian W. Tse, Elizabeth D. Williams, Brett G. Hollier. Monitoring tumor growth and oxygen distribution of prostate cancer xenografts in vivo using ultrasound and photoacoustic imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2855. doi:10.1158/1538-7445.AM2017-2855