A Macrophage-Specific Fluorescent Probe for Intraoperative Lymph Node Staging

Abstract

Successful identification of nodal metastases in patients with cancer is crucial to prescribe suitable treatment regimens that can improve recurrence-free survival. Although some new imaging technologies for nodal staging have been developed, such as nanoparticle-enhanced MRI and quantum-dot-based fluorescence imaging, sound technologies for intraoperative differentiation of metastatic and inflamed lymph nodes remain lacking. In this study, we illustrate the feasibility of using a macrophage-specific fluorescent probe (MFP) to visualize sentinel lymph nodes during surgery, highlighting abnormalities related to inflammation and tumor infiltration with signal enhancement and reduction methods using this technology. MFP was identified by high-throughput screening of fluorescent small-molecule libraries synthesized with a diversity-oriented approach. It selectively visualized monocyte and macrophage cell populations in vitro, by live-cell imaging and flow cytometry, as well as in vivo, for imaging-guided surgery. Collectively, this study provides preclinical proof of concept for an intraoperative imaging platform to accurately assess lymph node status, eliminating the need for invasive nodal dissections that can contribute to complications of cancer therapy. Cancer Res; 74(1); 44-55. Ó2013 AACR.

Advances in fluorescent-image guided surgery

“…A recent study highlighted the use of a novel macrophagespecific fluorescent probe for intraoperative lymph node staging (61). Discovered via a high-throughput screen, this probe selectively binds monocytes and macrophages, the latter of which are a main component of lymph nodes (61).…”

“…Discovered via a high-throughput screen, this probe selectively binds monocytes and macrophages, the latter of which are a main component of lymph nodes (61). A deficient fluorescent signal caused by the replacement of macrophages by disseminated tumor cells could therefore diagnose the precise location of a nodal metastasis (61).…”

“…Discovered via a high-throughput screen, this probe selectively binds monocytes and macrophages, the latter of which are a main component of lymph nodes (61). A deficient fluorescent signal caused by the replacement of macrophages by disseminated tumor cells could therefore diagnose the precise location of a nodal metastasis (61). Because of its unique binding property, this probe could be used not only to detect metastases in vivo but also to track local inflammation and adenopathy (61).…”

“…A deficient fluorescent signal caused by the replacement of macrophages by disseminated tumor cells could therefore diagnose the precise location of a nodal metastasis (61). Because of its unique binding property, this probe could be used not only to detect metastases in vivo but also to track local inflammation and adenopathy (61). Such studies lay the foundation for in vivo imaging technology that could eliminate unnecessary lymph node biopsies or dissections, reducing the postoperative complications of cancer therapies.…”

Fluorescent imaging of cancerous tissues for targeted surgery

“…Strategies include active targeting to HER2 receptor[149] and macrophages[150],as well as passive targeting by nanoparticles[151]. NIRF mapping of SLN with non-specific ICG has been used efficiently in breast cancer[152], lung cancer[153],melanoma[154, 155], and cervical cancer[156].…”