Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (5): 843-850. doi: 10.19723/j.issn.1671-167X.2023.05.011

Previous Articles     Next Articles

Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles

Zhan-yi ZHANG1,Fan ZHANG1,Ye YAN1,Cai-guang CAO2,Chang-jian LI3,Shao-hui DENG1,Yue-hao SUN1,Tian-liang HUANG1,Yun-he GUAN1,Nan LI4,Min LU5,Zhen-hua HU2,*(),Shu-dong ZHANG1,*()   

  1. 1. Department of Urology, Peking University Third Hospital, Beijing 100191, China
    2. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
    3. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Bei hang University, Beijing 100191, China
    4. Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing 100191, China
    5. Department of Pathology, Peking University Third Hospital, Beijing 100191, China
  • Received:2023-03-27 Online:2023-10-18 Published:2023-10-09
  • Contact: Zhen-hua HU,Shu-dong ZHANG E-mail:zhenhua.hu@ia.ac.cn;zhangshudong@bjmu.edu.cn
  • Supported by:
    the National Natural Science Foundation of China(82072828)

RICH HTML

 2   

PDF (PC)

66

Abstract:

Objective: To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats. Methods: A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures. Results: Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion. Conclusion: The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.

Key words: Molecular imaging, Indocyanine green, Prostatectomy, Erectile dysfunction, Sprague-Dawley rats

CLC Number: 

  • R699.8

Figure 1

Right-sided NVB of Sprague-Dawley male rats (×4) P, prostate; U, urethra; N(R), neurovascular bundles (NVB) (right-sided); asterisks depict the outline of cavernous nerve (CN) components in the NVB."

Figure 2

NIR-Ⅱ in vivo small animal imaging system and neuroimaging pattern of neurovascular bundles (NVB)"

Figure 3

Chemical structure formula and molecular weight of ICG-NP41"

Figure 4

In vitro fluorescence imaging of ICG-NP41 solution A, fluorescence images of a 2n-fold gradient diluted solution series at room temperature (adjusted to optimal contrast), stock solution concentration of 1 g/L (370 nmol/L), solvent PBS, exposure time 50 ms; B, in vitro fluorescence intensity curve of ICG-NP41 solution with various concentration."

Figure 5

In vivo imaging of prostatic neurovascular bundles (NVB) in rats (right-sided) A, white light (WL) and NIR-Ⅱ fluorescence imaging (FI) and pseudo-colour images of each group 2 h after immediate intraoperative tail vein administration; B, white light (WL) and NIR-Ⅱ fluorescence (FI) imaging and pseudo-colour images of each group 4 h after immediate intraoperative tail vein administration, and asterisks depict CN in the right NVB (Arrows depict the blood vessels in the NVB); C to H, SBR of CN with adjacent background tissues among different dose groups and time points; C, 2 mg/kg, 2 h post-injection; D, 2 mg/kg, 4 h post-injection; E, 4 mg/kg, 2 h post-injection; F, 4 mg/kg, 4 h post-injection; G, 3 groups, 2 h post-injection; H, 3 groups, 4 h post-injection."

Figure 6

Transverse section of the prostate urethra junction (cross section, HE ×100)"

1 Mazariego CG , Egger S , King MT , et al. Fifteen year quality of life outcomes in men with localised prostate cancer: Population based Australian prospective study[J]. BMJ, 2020, 371, 3503.
2 Schatloff O , Chauhan S , Sivaraman A , et al. Anatomic grading of nerve sparing during robot-assisted radical prostatectomy[J]. Eur Urol, 2012, 61 (4): 796- 802.
doi: 10.1016/j.eururo.2011.12.048
3 Song WH , Park JH , Tae BS , et al. Establishment of novel intraoperative monitoring and mapping method for the cavernous nerve during robot-assisted radical prostatectomy: Results of the phase Ⅰ/Ⅱ, first-in-human, feasibility study[J]. Eur Urol, 2020, 78 (2): 221- 228.
doi: 10.1016/j.eururo.2019.04.042
4 Yoon Y , Jeon SH , Park YH , et al. Visualization of prostatic nerves by polarization-sensitive optical coherence tomography[J]. Biomed Opt Express, 2016, 7 (9): 3170- 3183.
doi: 10.1364/BOE.7.003170
5 陈欣然, 王保军, 高宇, 等. 全息影像技术在机器人根治性前列腺切除术中的应用[J]. 中华泌尿外科杂志, 2021, 42 (7): 497- 501.
6 Mieog JSD , Achterberg FB , Zlitni A , et al. Fundamentals and developments in fluorescence-guided cancer surgery[J]. Nat Rev Clin Oncol, 2022, 19 (1): 9- 22.
doi: 10.1038/s41571-021-00548-3
7 Walsh EM , Cole D , Tipirneni KE , et al. Fluorescence imaging of nerves during surgery[J]. Ann Surg, 2019, 270 (1): 69- 76.
doi: 10.1097/SLA.0000000000003130
8 Whitney MA , Crisp JL , Nguyen LT , et al. Fluorescent peptides highlight peripheral nerves during surgery in mice[J]. Nat Biotechnol, 2011, 29 (4): 352- 356.
doi: 10.1038/nbt.1764
9 Hingorani DV , Whitney MA , Friedman B , et al. Nerve-targeted probes for fluorescence-guided intraoperative imaging[J]. Theranostics, 2018, 8 (15): 4226- 4237.
doi: 10.7150/thno.23084
10 Liu X, Lovell P, Cruz DR, et al. Novel intra-operative peripheral nerve agent for fluorescence guided imaging. Symposium on Clinical and Translational Neurophotonics 2020 held at SPIE BiO Conference, February 01, 2020[C]. San Francisco, CA: Spie-Int Soc Optical Engineering, 2020.
11 Chen Y , Zhang H , Lei Z , et al. Recent advances in intraoperative nerve bioimaging: Fluorescence-guided surgery for nerve preservation[J]. Small Struct, 2020, 1 (1): 2000036.
doi: 10.1002/sstr.202000036
12 Uetani H , Nakaura T , Kitajima M , et al. A preliminary study of deep learning-based reconstruction specialized for denoising in high-frequency domain: Usefulness in high-resolution three-dimensional magnetic resonance cisternography of the cerebellopontine angle[J]. Neuroradiology, 2021, 63 (1): 63- 71.
doi: 10.1007/s00234-020-02513-w
13 Antaris AL , Chen H , Diao S , et al. A high quantum yield molecule-protein complex fluorophore for near-infrared Ⅱ imaging[J]. Nat Commun, 2017, 8, 15269.
doi: 10.1038/ncomms15269
14 Hu Z , Fang C , Li B , et al. First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-Ⅰ/Ⅱ windows[J]. Nat Biomed Eng, 2020, 4 (3): 259- 271.
15 Qu Q , Nie H , Hou S , et al. Visualisation of pelvic autonomic nerves using NIR-Ⅱ fluorescence imaging[J]. Eur J Nucl Med Mol Imaging, 2022, 49 (13): 4752- 4754.
doi: 10.1007/s00259-022-05895-6
16 Glasgow HL , Whitney MA , Gross LA , et al. Laminin targeting of a peripheral nerve-highlighting peptide enables degenerated nerve visualization[J]. PNAS, 2016, 113 (45): 12774- 12779.
doi: 10.1073/pnas.1611642113
17 Hussain T , Nguyen LT , Whitney M , et al. Improved facial nerve identification during parotidectomy with fluorescently labeled peptide[J]. Laryngoscope, 2016, 126 (12): 2711- 2717.
doi: 10.1002/lary.26057
18 Jiang YF , Ngyen Q , Whitney M , et al. Vagal innervation of the esophagus and stomach: Visualized using a novel nerve peptide (NP41)[J]. Gastroenterology, 2017, 152 (5): S932.
19 You H , Shang W , Min X , et al. Sight and switch off: Nerve density visualization for interventions targeting nerves in prostate cancer[J]. Sci Adv, 2020, 6 (6): eaax6040.
doi: 10.1126/sciadv.aax6040
20 Haney NM , Nguyen HMT , Honda M , et al. Bilateral cavernous nerve crush injury in the rat model: A comparative review of pharmacologic interventions[J]. Sex Med Rev, 2018, 6 (2): 234- 241.
doi: 10.1016/j.sxmr.2017.07.007
21 Barth CW , Gibbs SL . Direct administration of nerve-specific contrast to improve nerve sparing radical prostatectomy[J]. Theranostics, 2017, 7 (3): 573- 593.
doi: 10.7150/thno.17433
[1] Hai MAO,Fan ZHANG,Zhan-yi ZHANG,Ye YAN,Yi-chang HAO,Yi HUANG,Lu-lin MA,Hong-ling CHU,Shu-dong ZHANG. Predictive model of early urinary continence recovery based on prostate gland MRI parameters after laparoscopic radical prostatectomy [J]. Journal of Peking University (Health Sciences), 2023, 55(5): 818-824.
[2] HE Wei,YANG Si-wen,CHEN Juan,ZHU Xiao-jun,CHEN Zhi-zhong,MA Wen-jun. Effects of 275 nm and 310 nm ultraviolet irradiation on bone metabolism in ovariectomized osteoporotic rats [J]. Journal of Peking University (Health Sciences), 2022, 54(2): 236-243.
[3] ZHANG Fan,CHEN Qu,HAO Yi-chang,YAN Ye,LIU Cheng,HUANG Yi,MA Lu-lin. Relationship between recovery of urinary continence after laparoscopic radical prostatectomy and preoperative/postoperative membranous urethral length [J]. Journal of Peking University (Health Sciences), 2022, 54(2): 299-303.
[4] HAO Han,LIU Yue,CHEN Yu-ke,SI Long-mei,ZHANG Meng,FAN Yu,ZHANG Zhong-yuan,TANG Qi,ZHANG Lei,WU Shi-liang,SONG Yi,LIN Jian,ZHAO Zheng,SHEN Cheng,YU Wei,HAN Wen-ke. Evaluating continence recovery time after robot-assisted radical prostatectomy [J]. Journal of Peking University (Health Sciences), 2021, 53(4): 697-703.
[5] ZHANG Fan,HUANG Xiao-juan,YANG Bin,YAN Ye,LIU Cheng,ZHANG Shu-dong,HUANG Yi,MA Lu-lin. Relationship between prostate apex depth and early recovery of urinary continence after laparoscopic radical prostatectomy [J]. Journal of Peking University (Health Sciences), 2021, 53(4): 692-696.
[6] Shu-dong ZHANG,Peng HONG,Bin-shuai WANG,Shao-hui DENG,Fan ZHANG,Li-yuan TAO,Cai-guang CAO,Zhen-hua HU,Lu-lin MA. Usefulness of the indocyanine green fluorescence imaging technique in laparoscopic partial nephrectomy [J]. Journal of Peking University (Health Sciences), 2020, 52(4): 657-662.
[7] Bing-wei HUANG,Jie WANG,Peng ZHANG,Zhe LI,Si-cheng BI,Qiang WANG,Cai-bo YUE,Kun-lin YANG,Xue-song LI,Li-qun ZHOU. Application of indocyanine green in complex upper urinary tract repair surgery [J]. Journal of Peking University (Health Sciences), 2020, 52(4): 651-656.
[8] ZHANG Fan, ZHANG Shu-dong, XIAO Chun-lei, HUANG Yi, MA Lu-lin. Perioperative parameters and prognosis analysis of patients aged 80 years or older treated with radical prostatectomy for prostate cancer [J]. Journal of Peking University(Health Sciences), 2018, 50(5): 822-827.
[9] ZHANG Fan, XIAO Chun-lei, ZHANG Shu-dong, HUANG Yi, MA Lu-lin. Relationship between recovery of urinary continence after laparoscopic radical prostatectomy and prostatic volume and intravesical prostatic protursion length [J]. Journal of Peking University(Health Sciences), 2018, 50(4): 621-625.
[10] ZHU Hua, WANG Feng,GUO Xiao-yi,LI Li-qiang, DUAN Dong-ban,LIU Zhi-bo, YANG Zhi . Preparation, quality control and thyroid molecule imaging of solid-target based radionuclide ioine-124 [J]. Journal of Peking University(Health Sciences), 2018, 50(2): 364-367.
[11] ZUO Qiang, ZHANG Fan, HUANG Yi, MA Lu-lin, LU Min, LU Jian. Clinically predictive factors of Gleason score upgrading in patients after radical prostatectomy [J]. Journal of Peking University(Health Sciences), 2016, 48(4): 603-606.
[12] YANG Jun, WANG Tao, ZHANG Yan, XU Hua, WANG Shao-Gang, LIU Ji-Hong, YE Zhang-Qun. Concentration of basic fibroblast growth factor in plasma and cavernous corpus of aged rat [J]. Journal of Peking University(Health Sciences), 2015, 47(4): 582-585.
[13] LIAO Xiao-Xing, XING Nian-Zeng, QIAO Peng, KANG Ning, ZHANG Jun-Hui, NIU Yi-Nong. "Sandwich” urethra reconstruction improves the early continence following laparoscopic radical prostatectomy [J]. Journal of Peking University(Health Sciences), 2015, 47(4): 601-604.
[14] LI Qing, XIAO Bo, LIU Shi-Jun, XU Tao, WANG Xiao-Feng. Effects of interval time between prostate biopsy and surgery on laparoscopic radical prostatectomy [J]. Journal of Peking University(Health Sciences), 2014, 46(4): 532-536.
[15] SHEN Qi, HU Shuai, LI Jun, WANG Jing-Hua, HE Qun. Incidence and clinicopathological characteristics of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens [J]. Journal of Peking University(Health Sciences), 2014, 46(4): 515-518.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd