Abstract
Early detection of metastasis is crucial for successful cancer treatment. Sentinel lymph node (SLN) biopsies are used to detect possible pathways of metastasis spread. We present a unique non-invasive diagnostic alternative to biopsy along with an intraoperative imaging tool for surgery proven on an in vivo animal tumor model. Our approach is based on mannan-based copolymers synergistically targeting: (1) SLNs and macrophage-infiltrated solid tumor areas via the high-affinity DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) receptors and (2) tumors via the enhanced permeability and retention (EPR) effect. The polymer conjugates were modified with the imaging probes for visualization with magnetic resonance (MR) and fluorescence imaging, respectively, and with poly(2-methyl-2-oxazoline) (POX) to lower unwanted accumulation in internal organs and to slow down the biodegradation rate. We demonstrated that these polymer conjugates were successfully accumulated in tumors, SLNs and other lymph nodes. Modification with POX resulted in lower accumulation not only in internal organs, but also in lymph nodes and tumors. Importantly, we have shown that mannan-based polymer carriers are non-toxic and, when applied to an in vivo murine cancer model, and offer promising potential as the versatile imaging agents.
Highlights
It is widely known that cancer is one of the leading causes of death worldwide, and despite the huge progress in cancer treatment over the recent years, many of the mechanisms involved in the complex process of tumor and especially metastasis development are still not fully understood
Various methods are used for metastasis and sentinel lymph node (SLN) detection, including standard blue-dye intraoperative detection and imaging methods such as magnetic resonance imaging (MRI) [5,6,7], ultrasound [8], single-photon emission computed tomography (SPECT), fluorescence, lymphoscintigraphy, and others [9,10]
As a complementary imaging method providing no attenuation of the signals in dependence to the tissue localization, we used a standard and non-invasive method routinely used both in experimental medicine and clinical practice: 1 H-MRI
Summary
It is widely known that cancer is one of the leading causes of death worldwide, and despite the huge progress in cancer treatment over the recent years, many of the mechanisms involved in the complex process of tumor and especially metastasis development are still not fully understood. To address this deficit, efforts are being made to more precisely diagnose and treat metastasis spreading. As an alternative to ALN dissection, sentinel lymph node (SLN) biopsy is used as a standard clinical procedure [1,2,3]. Each method provides different information, and comes with limitations, e.g., the low specificity of MRI and the optical signal attenuation
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