title: Ultrasensitive in vivo detection of primary gastric tumor and lymphatic metastasis using upconversion nanoparticles.
abstract: Lymphatic metastasis is an important prognostic factor regarding long-term survival rate of gastric cancer (GC) patients. Pretreatment knowledge of lymph node status is extremely helpful for planning treatment and prognosis. However, to date, no imaging method has been demonstrated to be effective for detecting lymphatic metastasis in GC. Molecular imaging probes based on upconversion nanoparticles with unique optical and magnetic properties have provided great hope for early tumor detection. Herein we report highly sensitive detection of lymphatic spread using core@shell structured NaGdF4:Yb,Er@NaGdF4 upconversion nanoparticles coated with polyethylene glycol (PEG). A GC-specific probe was constructed through "click" reaction between the maleimide moiety of PEG ligand and the thiol group from partly reduced antigastric cancer antibody MGb2. The primary tumor and adjacent lymphatic metastasis site were clearly differentiated by upconversion luminescence imaging after the GC-specific probe was delivered through tail vein injection into tumor-bearing mice. Moreover, lymphatic metastases smaller than 1 mm were successfully detected, owing to the ultralow background under 980 nm excitation. It has been demonstrated that both primary and lymphatic metastatic sites in an orthotopic mouse model of human gastric cancer can be optically detected by using GC-specific upconversion luminescence nanoprobes. The current studies may therefore provide a highly effective approach for GC diagnosis.
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences , Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Qiao
authors.forename: Changhao
authors.initials: C
authors.lastname: Liu
authors.forename: Muhan
authors.initials: M
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Hou
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Yenan
authors.initials: Y
authors.lastname: Lin
authors.forename: Jimin
authors.initials: J
authors.lastname: Liang
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Gao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004871:Erbium / Q000737:chemistry; D005260:Female; D005459:Fluorides / Q000737:chemistry; D006801:Humans; D049449:Luminescence; D008207:Lymphatic Metastasis; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging; D011092:Polyethylene Glycols / Q000737:chemistry; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000473:pathology*; D015018:Ytterbium / Q000737:chemistry
chemical_list: D015335:Molecular Probes; D011092:Polyethylene Glycols; D004871:Erbium; D015018:Ytterbium; D005459:Fluorides
keywords: gastric cancer; lymphatic metastasis; molecular imaging; ultrasensitive detection; upconversion nanoparticles