title: SPECT and near-infrared fluorescence imaging of breast cancer with a neuropilin-1-targeting peptide.
abstract: Breast cancer is the most common malignant cancer and is the leading cause of cancer death among females. Molecular imaging is a promising approach for the early detection and staging of breast cancer as well as for assessing therapeutic responses. Tumor-targeting peptides are effective targeting vehicles for molecular imaging. Here, we identified a breast cancer-targeting peptide CLKADKAKC (CK3) contains a cryptic C-end rule motif that may mediate its binding to neuropilin-1 (NRP-1), an attractive therapeutic target which expression was associated with poor outcome of the patients with breast cancer. Phage CK3 bound to NRP-1-positive breast cancer cells, which could be inhibited by peptide CK3 in a dose-dependent manner or by knock-down NRP-1 expression. Consistently, NRP-1 overexpression in cells increased the binding of phage CK3. Furthermore, peptide CK3 co-localized with NRP-1. Importantly, unlike previously reported NRP-1-targeting peptides with exposed C-end rule motifs, peptide CK3 did not penetrate into lungs and heart in vivo, which could make it more clinically applicable. Single-photon emission CT (SPECT) and near-infrared fluorescence (NIRF) imaging showed enrichment of peptide CK3 to the xenograft tumors in nude mice. In conclusion, as a novel NRP-1-targeting peptide, peptide CK3 could be used for breast cancer molecular imaging, which may represent a new avenue for breast cancer diagnostics, staging and assessments of therapeutic response.
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
authors: Guo-Kai
authors: GK
authors: Feng
authors: Department of Nuclear Medicine, The Second Affiliated Hospital of Guangzhou Medicine University, Guangzhou 510260, Guangdong, China.
authors: Rong-Bin
authors: RB
authors: Liu
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
authors: Meng-Qing
authors: MQ
authors: Zhang
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
authors: Xiao-Xuan
authors: XX
authors: Ye
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
authors: Qian
authors: Q
authors: Zhong
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
authors: Yun-Fei
authors: YF
authors: Xia
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China.
authors: Man-Zhi
authors: MZ
authors: Li
authors: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Anhui 230027, Hefei, China.
authors: Jun
authors: J
authors: Wang
authors: Breast Cancer Center of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong, China.
authors: Er-Wei
authors: EW
authors: Song
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China. Electronic address: zhangxing@sysucc.org.cn.
authors: Xing
authors: X
authors: Zhang
authors: Department of Nuclear Medicine, The Second Affiliated Hospital of Guangzhou Medicine University, Guangzhou 510260, Guangdong, China. Electronic address: wu_zhaozhong@126.com.
authors: Zhao-Zhong
authors: ZZ
authors: Wu
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China. Electronic address: zengmsh@sysucc.org.cn.
authors: Mu-Sheng
authors: MS
authors: Zeng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods; D008969:Molecular Sequence Data; D039942:Neuropilin-1 / Q000032:analysis* / Q000378:metabolism; D061848:Optical Imaging / Q000379:methods; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D010455:Peptides; D039942:Neuropilin-1
keywords: Breast Cancer; NIRF; Neuropilin-1; Phage display; SPECT; tumor targeting-peptide