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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. ©2013 AACR.

PDF file - 5664K, Supplementary Figure 1: Overview of high-throughput screening, Supplementary Figure 2: Synthesis scheme for MFP, Supplementary Figure 3: Identification spectra of MFP obtained by using 1H-NMR and 13C-NMR, Supplementary Figure 4: Identification LC-MS spectrum of MFP, Supplementary Figure 5: Physiochemical properties of MFP, Supplementary Figure 6: Macrophage differentiation with the U-937 cell line by using PMA stimulation, Supplementary Figure 7: Selective macrophage staining with MFP for different concentrations and incubation times, Supplementary Figure 8: Effect of MFP on cell viability, Supplementary Figure 9: Enrichment of T lymphocytes, monocytes and granulocytes from human blood, Supplementary Figure 10: Macrophage differentiation with peripheral blood monocytes, Supplementary Figure 11: Characterization of MFP+ cells in inflamed lymph nodes, Supplementary Figure 12: Characterization of MFP+ cells in metastatic lymph nodes, Supplementary Figure 13: Structural selectivity test with several analogues of MFP, Supplementary Methods.

(9Z,11E)-tetradecadienyl acetate (9Z,11E-14:OAc) and (3Z,6Z,9Z,12Z,15Z)-pentacosapentaene (C25 pentaene), known as the sex pheromone of the European Dioryctria abietella population, were identified in the Korean D. abietella population. The ratio of 9Z,11E-14:OAc to C25 pentaene extracted from female pheromone glands was 1:23. The electroantennogram (EAG) response of male antennae to 9Z,11E-14:OAc was stronger than to C25 pentaene, whereas an opposite EAG response was observed in female antennae. Major volatile compounds in mature Korean pine cone (Pinus koraiensis), such as limonene, myrcene, and (-)-α-pinene, elicited dose-dependent EAG responses of male and female antennae. In field attraction testing, traps baited with 100:1,000, 100:2,000, and 100:3,000 ug of 9Z,11E-14:OAc to C25 pentaene were the most attractive to male D. abietella. More males were attracted to traps baited with 9Z,11E-14:OAc+C25 pentaene+limonene than traps baited with 9Z,11E-14:OAc+C25 pentaene. This showed that limonene acted as a synergist to sex pheromone. Delta traps, wing traps, and diamond traps were superior to bucket traps for capturing D. abietella males. This study showed that pheromone traps baited with 100:1,000 ~ 100:3,000 ug of 9Z,11E-14:OAc to C25 pentaene and limonene will be useful for the exact monitoring of D. abietella flight phenology in Pinus koraiensis Sieb. & Zucc. (Pinales: Pinaceae) forests.