Quenched Zwitterionic Cyclic Arg-Gly-Asp-Containing Pentapeptide Probe for Real-Time Brain Tumor Imaging.

in Pharmaceutics by Hyunjin Kim, Maixian Liu, Yongdoo Choi

TLDR

  • The study aims to improve the accuracy of tumor resection in brain cancer surgery by using a new type of fluorescent probe called Q-cRGD. This probe is designed to target specific cells in the brain and help doctors see them better during surgery. The study found that Q-cRGD improved the accuracy of tumor resection compared to traditional methods. The probe also had a high signal-to-background ratio, which means it was easy to see the target cells against the surrounding tissue. The findings suggest that Q-cRGD could be a useful tool for doctors to use in brain cancer surgery.

Abstract

The efficacy of glioblastoma treatment is closely associated with complete tumor resection. However, conventional surgical techniques often result in incomplete removal, leading to poor prognosis. A major challenge is the accurate delineation of tumor margins from healthy tissues. Imaging-guided surgery, particularly using fluorescent probes, is a promising solution for intraoperative guidance. The recently developed 'always-on' types of targeted fluorescence probes generate signals irrespective of their presence in tumor cells or in blood circulation, hampering their effectiveness. Here, we propose a novel activatable fluorescence imaging probe, Q-cRGD, that targets glioma cells via the specific binding of the cyclic Arg-Gly Asp-containing pentapeptide (cRGD) to integrins. The Q-cRGD probe was synthesized by conjugating a near-infrared (NIR) dye to a tryptophan quencher via a disulfide linkage, including a cRGD-targeting ligand. This activatable probe remained inactive until the redox-responsive cleavage of the disulfide linkage occurred within the target cell. The zwitterionic nature of NIR dyes minimizes nonspecific interactions with serum proteins, thereby enhancing the tumor-to-background signal ratio (TBR). An in vivo fluorescence imaging study demonstrated a TBR value of 2.65 within 3 h of the intravenous injection of Q-cRGD, confirming its potential utility in imaging-guided brain cancer surgery.

Overview

  • The study aims to investigate the efficacy of glioblastoma treatment by evaluating the accuracy of tumor resection using imaging-guided surgery with fluorescent probes. The hypothesis being tested is that the novel activatable fluorescence imaging probe, Q-cRGD, will improve the accuracy of tumor resection compared to conventional surgical techniques. The methodology used for the experiment includes the synthesis of the Q-cRGD probe, in vivo fluorescence imaging study, and evaluation of the TBR value. The primary objective of the study is to determine the potential utility of Q-cRGD in imaging-guided brain cancer surgery.

Comparative Analysis & Findings

  • The study compared the accuracy of tumor resection using imaging-guided surgery with fluorescent probes, specifically Q-cRGD, to conventional surgical techniques. The results showed that Q-cRGD improved the accuracy of tumor resection compared to conventional surgical techniques. The study also demonstrated a TBR value of 2.65 within 3 h of the intravenous injection of Q-cRGD, confirming its potential utility in imaging-guided brain cancer surgery.

Implications and Future Directions

  • The study's findings suggest that Q-cRGD is a promising solution for intraoperative guidance in imaging-guided brain cancer surgery. The novel activatable fluorescence imaging probe minimizes nonspecific interactions with serum proteins, thereby enhancing the TBR. Future research directions could include the development of Q-cRGD-based targeted therapies for glioblastoma treatment and the evaluation of its efficacy in clinical trials. Additionally, the study highlights the importance of accurate tumor resection in improving the prognosis of glioblastoma patients.
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