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The Journal of surgical research

Fluorescent-tilmanocept for tumor margin analysis in the mouse model.


PMID 24923630

Abstract

Dendritic cells (DC) are localized in close proximity to cancer cells in many well-known tumors, and thus maybe a useful target for tumor margin assessment. [(99m)Tc]- cyanine 7 (Cy7)-tilmanocept was synthesized and inxa0vitro binding assays to bone marrow-derived DC were performed. Fifteen mice, implanted with either 4T1 mouse mammary or K1735 mouse melanoma tumors, were administered 1.0xa0nmol of [(99m)Tc]-Cy7-tilmanocept via tail vein injection. After fluorescence imaging 1 or 2xa0h after injection, the tumor, muscle, and blood were assayed for radioactivity to calculate percent-injected dose. Digital images of the tumors after immunohistochemical staining for DC were analyzed to determine DC density. Inxa0vitro binding demonstrated subnanomolar affinity of [(99m)Tc]-Cy7-tilmanocept to DC (KA =xa00.31xa0±xa00.11xa0nM). After administration of [(99m)Tc]-Cy7-tilmanocept, fluorescence imaging showed a 5.5-fold increase in tumor signal as compared with preinjection images and a 3.3-fold difference in fluorescence activity when comparing the tumor with the surgical bed after tumor excision. Immunohistochemical staining analysis demonstrated that DC density positively correlated with tumor percent of injected dose per gram (rxa0=xa00.672, Pxa0=xa00.03), and higher DC density was observed at the periphery versus center of the tumor (186xa0±xa054xa0K versus 64xa0±xa016xa0K arbitrary units, Pxa0=xa00.001). [(99m)Tc]-Cy7-tilmanocept exhibits inxa0vitro and inxa0vivo tumor-specific binding to DC and maybe useful as a tumor margin targeting agent.