Department of Surgery, University of San Diego, California.
Department of Radiology, University of San Diego, California; In Vivo Cancer and Molecular Imaging Center, University of San Diego, California.
J Surg Res. 2014 Aug;190(2):528-34. doi: 10.1016/j.jss.2014.05.012. Epub 2014 May 10.
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 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.
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).
[(99m)Tc]-Cy7-tilmanocept exhibits in vitro and in vivo tumor-specific binding to DC and maybe useful as a tumor margin targeting agent.
树突状细胞 (DC) 在许多著名肿瘤中与癌细胞密切相邻，因此可能是评估肿瘤边界的有用靶标。
合成 [(99m)Tc]-半花菁 7（Cy7）-tilmanocept 并进行骨髓来源的 DC 的体外结合测定。15 只小鼠，植入 4T1 小鼠乳腺癌或 K1735 小鼠黑色素瘤肿瘤，尾静脉注射 1.0 nmol [(99m)Tc]-Cy7-tilmanocept。注射后 1 或 2 小时进行荧光成像，测定肿瘤、肌肉和血液中的放射性以计算注入的放射性剂量百分比。对 DC 免疫组织化学染色后的肿瘤进行数字图像分析，以确定 DC 密度。
体外结合研究表明 [(99m)Tc]-Cy7-tilmanocept 与 DC 的亲和力为亚纳摩尔级（KA = 0.31 ± 0.11 nM）。给予 [(99m)Tc]-Cy7-tilmanocept 后，荧光成像显示与注射前图像相比，肿瘤信号增加了 5.5 倍，与肿瘤切除后手术床相比，荧光活性增加了 3.3 倍。免疫组织化学染色分析表明，DC 密度与肿瘤每克注入剂量的百分比呈正相关（r = 0.672，P = 0.03），并且在肿瘤的外围观察到比中心更高的 DC 密度（186 ± 54 K 与 64 ± 16 K 任意单位，P = 0.001）。
[(99m)Tc]-Cy7-tilmanocept 在体外和体内均显示出对 DC 的肿瘤特异性结合，可能是一种有用的肿瘤边界靶向剂。
