Targeted imaging of orthotopic prostate cancer by using clinical transformable photoacoustic molecular probe

Chen Qiu,Xiaoyan Miao,Tinghui Yin,Yuanyuan Bai,Jie Ren,Liang Song,Chengbo Liu,Huichao Zhou,Rongkang Gao,Rongqin Zheng,Hairong Zheng

doi:10.1186/s12885-020-06801-9

Abstract

BackgroundTo obtain high-yield histological samples by targeted prostate cancer (PCa) biopsy is the current trend compared with transrectal ultrasound (TRUS)-guided systematic histological biopsy, which is regarded as the gold standard for prostate cancer (PCa) diagnosis. In this paper, we present a targeted PCa imaging strategy using a real-time molecular photoacoustic imaging system integrated with a handheld US probe (PAI/US) and synthesized an integrin αvβ3 targeted probe based on ICG (cRGD–ICG).MethodsTo prepare cRGD–ICG, ICG-NHS was linked to cRGD through carboxyl-co-reaction. In vitro PA imaging ability of cRGD–ICG was tested. Orthotopic PCa-bearing rats were used as animal models. After injected with either cRGD–ICG or non-targeted probe, rats were implemented with PA imaging to confirm the specific accumulation of cRGD–ICG at tumor region. Moreover, pathological frozen slices were made to observe distribution of the probe in prostate tissue ex vivo.ResultsA small molecular PAI probe was synthesized and exhibited excellent targeted imaging ability in vitro. In vivo photoacoustic imaging was carried out after intravenous injection of cRGD-ICG in orthotopic PCa-bearing rats under the facilitation of the PAI/US system. Maximum molecular photoacoustic signals were observed in the tumor area in vivo after the probe injection, which showed 3.8-fold higher signal enhancement than that in the control group (P < 0.05). Significantly higher cRGD-ICG accumulation was observed under confocal microscopy in the tumor region than in normal prostate tissue.ConclusionsAll our results showed that the comprehensive strategy provided a high-yield and reliable method for PCa diagnosis and targeted prostate biopsy, with great clinical translation potential.

Highlights

To obtain high-yield histological samples by targeted prostate cancer (PCa) biopsy is the current trend compared with transrectal ultrasound (TRUS)-guided systematic histological biopsy, which is regarded as the gold standard for prostate cancer (PCa) diagnosis
At 795 nm, the in vitro Photoacoustic imaging (PAI) properties of the molecular probe were tested at different concentrations (1.25–20 μg/ml), and the results are shown in Fig. 2c and d. Cyclic arginineglycine-aspartic acid sequence (cRGD)-indocyanine green (ICG) displayed a stable linear PAI signal increase as the concentration was increased linearly from 1.25 to 20 μg/ml
After incubating 50% of Human umbilical vein endothelial cells (HUVEC) with a targeted agent and another 50% with a nontargeted agent, cells were collected for flow cytometry

Summary

Introduction

To obtain high-yield histological samples by targeted prostate cancer (PCa) biopsy is the current trend compared with transrectal ultrasound (TRUS)-guided systematic histological biopsy, which is regarded as the gold standard for prostate cancer (PCa) diagnosis. Systematic histological biopsy guided by transrectal ultrasound (TRUS) has been regarded as the gold standard procedure for diagnosing PCa [2]. Since the sensitivity and specificity of the US method to identify malignancies are relatively low, US is mainly used to provide anatomical reference within the prostate while performing a systemic biopsy. In the mpMRI technique, suspicious regions identified in MRI are targeted for biopsy under US guidance using fusion imaging. This technique is still too expensive to afford, along with a 5–15% false-negative cancer detection rate [5]. This approach is limited by the detectability of PCa-targeted biopsy

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Discussion

Conclusion