Photoacoustic imaging of prostate cancer using cylinder diffuse radiation

To pave the road toward clinical application of photoacoustic imaging in prostate cancer (PCa) diagnosis, we studied the technical feasibility and performance of transrectal photoacoustic (PA) imaging in mapping the indocyanine green (ICG) contrast agent, which is approved by FDA, in entire prostates by using light illumination via the urethral track. Experiments were conducted on a clinically relevant ex vivo model involving whole human prostates harvested from radical prostatectomy. The light source placed in the urethral track was an array of light emitting diodes (LEDs), illuminating the prostate with a delivered light power on the urethral wall within the safety limit. A dual-modality imaging system acquired PA and ultrasound (US) images simultaneously in the same way as in transrectal ultrasound (TRUS), with the US imaging presenting the tissue structure and PA imaging detecting the ICG solution. The imaging results demonstrated that tubes containing ICG solution at different concentrations can be detected at different positions in the prostate within a 2 cm range around from the urethral wall. Considering the sizes of regular human prostates, the proposed transurethral illumination in combination with transrectal US detection can facilitate PA molecular imaging over the entire prostate in a non-invasive manner, which makes it possible to further improve the PCa diagnosing efficiency with better molecular sensitivity and resulted better biopsy accuracy and much reduced pain for patients. Impact statement Differentiating cancerous tissues from healthy ones is critical in the diagnosis of prostate cancer (PCa). However, due to the low sensitivity of ultrasound (US) imaging to cancerous tissues, transrectal ultrasound (TRUS) guided biopsies, current standard procedure for diagnosing PCa, suffer from low core yield, leading to under-sampling and under-grading of clinically significant tumors. Via the experiment on the ex vivo human prostates, we evaluated the translational potential of photoacoustic imaging (PAI) based on a safe light emitting diodes (LED) source for detecting the molecular information in deep human prostate. We showed that transurethral light illumination in combination with transrectal US detection can facilitate PA molecular imaging over an entire human prostate in a non-invasive manner. The success of this study in the clinically relevant ex vivo human prostate model suggested a new strategy for PA and US combined imaging and detection of PCa.

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Targeted Imaging of Orthotopic Prostate Cancer by Using Clinical Transformable Photoacoustic Molecular Probe

10.21203/rs.2.18703/v2 ◽

2020 ◽

Author(s):

Chen Qiu ◽

Yuanyuan Bai ◽

Tinghui Yin ◽

Xiaoyan Miao ◽

Rongkang Gao ◽

...

Keyword(s):

Prostate Cancer ◽

Imaging System ◽

Photoacoustic Imaging ◽

Current Trend ◽

Molecular Probe ◽

High Yield ◽

Control Group ◽

Targeted Imaging ◽

Normal Prostate

Abstract Background: 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. 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 α v β 3 targeted probe based on ICG (cRGD–ICG). Results: A 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. Conclusions: All 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.

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Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and Treatment of Prostate Cancer

10.21203/rs.2.24286/v1 ◽

2020 ◽

Author(s):

Minmin Lan ◽

Lianhua Zhu ◽

Yixuan Wang ◽

Dajia Shen ◽

Kejing Fang ◽

...

Keyword(s):

Prostate Cancer ◽

Indocyanine Green ◽

Ultrasound Imaging ◽

Multimodal Imaging ◽

Photoacoustic Imaging ◽

Drug Loading ◽

Tissue Imaging ◽

Tumor Xenografts

Abstract Background: Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and high resolution, thereby enabling rapid and direct measurement and tracking of tumor growth and metastasis. At the same time, ultrasound targeted nanobubble destruction (UTND) provides an effective way to drug accumulation; effectively increasing the content of the drug in the tumor area and reducing potential side effects, thereby contributing effectively to the treatment of the tumors.Result: In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs), and study their application in ultrasound imaging of prostate cancer as well as their therapeutic effect on prostate cancer when combined with ultrasound targeted nanobubble destruction (UTND). ICG-PTX NBs were prepared by mechanical oscillation method. Their particle size and Zeta potential of ICG-PTX NBs were 469.5±32.87 nm and -21.70±1.222 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 6.2%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect is positively correlated with their concentration. The imaging effect of tumor xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumor xenografts in vivo, the ICG-PTX NBs+US group showed more significant inhibition of cell proliferation and promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs group and the ICG-PTX NBs+US group were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organ showed no obvious abnormalities in the ICG-PTX NBs group and the ICG-PTX NBs+US group.Conclusions: ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent for both diagnosis and treatment that can achieve enhanced imaging, effective inhibition and killing of prostate cancer under the guidance of multimodal imaging including ultrasound, fluorescence and photoacoustic imaging.

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