1. Mannosylated Dextran Derivatives as Bimodal Imaging Probes for Sentinel Lymph Node Detection Synthesis Characterization Biological Evaluation in Wistar Rats Sentinel lymph node detection (SLND) is very important for cancer management and to establish adequate therapy. 1 99m Tc-based radiopharmaceuticals and blue dyes are used for pre- and intraoperative SLND, despite having properties far from ideal. 2 Radiolabeled mannosylated nanoparticles have been successfully explored for SLN imaging and, recently, 99m Tc-DTPA-labeled dextran ( 99m Tc-Tilmanocept) has been approved by FDA for SLND in melanoma and breast cancer. 3-10 Herein, we present our results on two bimodal mannosylated dextran nanocompounds for pre- and intraoperative SLND by nuclear ( 99m Tc or 68 Ga) and optical imaging (NIR). Background and Aim Optical Imaging in Wistar Rats Maurício Morais, 1 M. P. C. Campello, 1 Catarina Xavier, 2 Sophie Hernot, 2 João D. G. Correia, 1 Tony Lahoutte, 2,3 Vicky Caveliers 2,3 and Isabel Santos 1 1 Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Portugal; email: isantos@ctn.ist.utl.pt 2 In Vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel, Brussels, Belgium 3 Nuclear Medicine Department, UZ Brussel, Brussels, Belgium 1. Sharma, R., et al., Ann Ny Acad Sci. 2008; 1131:13-36. 2. Ravizzini, G., et al., Wires Nanomed Nanobi. 2009; 1:610-23. 3. Vera DR, et al., J Nucl Med. 1997; 38:530-5. 4. J. Nucl. Med. 2013; 20N. 5. Ting R, et al., Bioconjugate Chem. 2010; 21:1811-9. Fundação para a Ciência e Tecnologia (FCT) is acknowledged for financial support (EXCL/QEQ-MED/0233/2012). Maurício Morais thanks FCT for a PhD grant (SFRH/BD/48066/2008) and COST Action TD1004 for the COST STSM- TD1004-040213-027456.  99m Tc- or 68 Ga- mannosylated dextran containing NIR fluorophores were synthesized in high yield and radiochemical purity.  These bimodal probes were fully characterized from the physicochemical point of view.  Biological evaluation in rats has shown that both probes presented high popliteal extraction (P.E.) values (≥ 90 %).  Nuclear radiation and NIR fluorescence signal complement each other in the detection and excision of sentinel lymph node. Vrije Universiteit Brussel Bright field (left) and NIR optical imaging (right) image of a Wistar rat leg injected with 3 or 5 (1 nmol; exposure time 350 ms), at 1 h p.i. The yellow arrow indicates the localization of the dual tracer in the popliteal lymph node. 1 3: M = 99m Tc; 4: M = Re Animal 2 2 5: M = 68 Ga; 6: M = Ga 68 GaCl 3, 5 min, 100 ºC or Ga(NO 3 ) 3, 18h, 50ºC Emission Spectra Size distribution by dynamic light scattering 4 : 22.5 ± 2.9 nm 6 : 50.8 ± 8.1 nm 826 nm Blood 0.82 ± 0.54 Liver 1.48 ± 0.15 Intestine 0.52 ± 0.08 Kidney 0.23 ± 0.15 Spleen 0.01 ± 0.00 Bladder 0.14 ± 0.02 1 st LN 1.01 ± 0.26 2 nd LN 0.10 ± 0.54 I. S. 92.82 ± 0.94 P.E. (%) 91 Tissue/organ% IA/organ ± SD 1 st LN 2 nd LN Bladder I.S. PET/CT image of Wistar rat injected with 5 at 1 h p.i.. Biodistribution data of 5 after 1 h p.i. 1 st LN I.S. Blood 0.23 ± 0.20 Liver 1.81 ± 0.46 Intestine 0.34 ± 0.17 Kidney 0.46 ± 0.1 Spleen 0.02 ± 0.01 Bladder 0.02 ± 0.01 1 st LN 3.87 ± 0.63 2 nd LN 0.36 ± 0.21 Inj.site (I.S.) 86.72 ± 0.92 P.E. (%) 90 Tissue/organ% IA/organ ± SD Biodistribution data of 3 after 3 h p.i. SPECT/CT images of Wistar rat injected with 3 at 3 h p.i.. 3 [ 99m Tc(CO) 3 (H 2 O) 3 ] +, 10 min, 100 ºC or [Re(CO) 3 (H 2 O) 3 ]Br, 18 h, 50 ºC 6. Morais M., et al., Mol. Pharm., 2011; 8, 609-620. 7. Ocampo-Garcia B.E., et al., Nucl Med Biol. 2011; 38, 1-11 8. Ting R, et al., Bioconjugate Chem. 2010; 21:1811-9. 9. Emerson DK, et al., Radiology. 2012; 265:186-93. 10. Qin Z, et al., J Biomed Opt. 2013; 18:101315. 5 Concluding Remarks Acknowledgments 4 6