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

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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)

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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)"

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