Adochite Ramona-Cosmina, Moshnikova Anna, Golijanin Jovana, Andreev Oleg A, Katenka Natallia V, Reshetnyak Yana K
Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA.
Department of Computer Sciences and Statistics, University of Rhode Island, 9 Greenhouse Road, Kingston, RI, 02881, USA.
Mol Imaging Biol. 2016 Oct;18(5):686-96. doi: 10.1007/s11307-016-0949-6.
Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.
Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP(®) variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP(®) variants in multidimensional space of spectral parameters.
The fluorescently labeled pHLIP(®) variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP(®) peptide.
Different cargo molecules conjugated with pHLIP(®) peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP(®)-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.
细胞外空间酸化促进肿瘤发展、进展和侵袭性。pH（低）插入肽（pHLIP®肽）属于pH敏感膜肽类，其靶向酸性肿瘤并将成像和/或治疗剂递送至肿瘤内的癌细胞。
对在给予与各种极性荧光染料偶联的不同pHLIP®变体后不同时间点收集的组织和器官进行离体荧光成像。采用多变量统计分析方法在光谱参数的多维空间中建立荧光标记的pHLIP®变体之间的分类。
基于其生物分布概况和靶向原发性肿瘤的能力对荧光标记的pHLIP®变体进行分类。此外，静脉注射荧光pHLIP®肽后通过离体成像鉴定出肺部亚毫米大小的转移病灶。
与pHLIP®肽偶联的不同货物分子可改变生物分布和肿瘤靶向性。所获得的知识对于设计基于pHLIP®的新型诊断和治疗剂以靶向原发性肿瘤和转移病灶至关重要。
