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Published on: January 19, 2018
Fluorescent-tilmanocept for tumor margin analysis in the mouse model
Ava Hosseini1, Jennifer L Baker1, Christopher A Tokin1
1Department of Surgery, University of San Diego, California.
Background:
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.
Materials And Methods:
[(99m)Tc]- cyanine 7 (Cy7)-tilmanocept was synthesized and in vitro binding assays to bone marrow-derived DC were performed. Fifteen mice, implanted with either 4T1 mouse mammary or K1735 mouse melanoma tumors, were administered 1.0 nmol of [(99m)Tc]-Cy7-tilmanocept via tail vein injection. After fluorescence imaging 1 or 2 h 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.
Results:
In vitro binding demonstrated subnanomolar affinity of [(99m)Tc]-Cy7-tilmanocept to DC (KA = 0.31 ± 0.11 nM). 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 (r = 0.672, P = 0.03), and higher DC density was observed at the periphery versus center of the tumor (186 ± 54 K versus 64 ± 16 K arbitrary units, P = 0.001).
Conclusions:
[(99m)Tc]-Cy7-tilmanocept exhibits in vitro and in vivo tumor-specific binding to DC and maybe useful as a tumor margin targeting agent.
Insights
[(99m)Tc]-Cy7-tilmanocept shows specific binding to dendritic cells (DC) in vitro and in vivo. This agent may be useful for assessing tumor margins, aiding in surgical precision.
Area of Science:
- Oncology
- Radiochemistry
- Immunology
Background:
- Dendritic cells (DCs) are present near tumor cells in many cancers.
- DCs may serve as a target for evaluating tumor margins.
Purpose of the Study:
- To synthesize [(99m)Tc]-cyanine 7 (Cy7)-tilmanocept.
- To evaluate the in vitro and in vivo binding of [(99m)Tc]-Cy7-tilmanocept to dendritic cells (DCs) for potential use as a tumor margin assessment agent.
Main Methods:
- Synthesis of [(99m)Tc]-Cy7-tilmanocept and in vitro binding assays with bone marrow-derived DCs.
- Administration of the agent to mice with 4T1 mammary or K1735 melanoma tumors, followed by fluorescence imaging.
- Radioactivity measurements and immunohistochemical staining to determine DC density and correlate it with agent uptake.
Main Results:
- [(99m)Tc]-Cy7-tilmanocept demonstrated subnanomolar affinity for DCs in vitro.
- Fluorescence imaging revealed increased tumor signal post-injection, with higher activity in tumors compared to surgical beds.
- DC density positively correlated with the injected dose per gram in tumors, with higher density observed at the tumor periphery.
Conclusions:
- [(99m)Tc]-Cy7-tilmanocept exhibits specific in vitro and in vivo binding to DCs.
- The agent shows potential as a valuable tool for tumor margin targeting and assessment in cancer surgery.
