title: Evaluation of68Ga-labeled iNGR peptide with tumor-penetrating motif for microPET imaging of CD13-positive tumor xenografts.
abstract: The aim of the study is to evaluate the efficacy of68Ga-labeled iNGR, containing Asn-Gly-Arg (NGR) homing sequence and CendR (R/KXXR/K) penetrating motif, as a new molecular probe for microPET imaging of CD13-positive xenografts. The synthesized iNGR and NGR peptides were conjugated with DOTA and then labeled with68Ga.68Ga-iNGR and68Ga-NGR were compared in the performance of the in vitro stability, partition coefficient, binding affinity, cell uptake analysis, in vivo microPET imaging, and biodistribution studies in CD13-positive HT-1080 and CD13-negative HT-29 cell lines. The in vitro results revealed that both probes exhibited high radiochemical purity and stability, and no significant difference between two probes was observed in terms of the binding affinity to CD13. In vivo microPET/CT imaging showed that the uptake of68Ga-iNGR in HT-1080 tumor was significantly higher than that of68Ga-NGR. Moreover, tumor68Ga-iNGR uptake could be completely blocked by cold NGR and partially blocked by neutralizing NRP-1 antibody. We concluded that68Ga-iNGR has a higher tumor uptake and better tumor retention than68Ga-NGR through NRP-1, indicating that CendR motif modification is a promising method for improving NGR peptide performance.
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China.|Department of Nuclear Medicine, Kunming General Hospital of the People's Liberation Army, No. 212 Daguan Road, Kunming, 650032, China.
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China.
authors.forename: Mingru
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China. fmmukf@qq.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Kang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, 710032, China. wangjing@fmmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D018826:CD13 Antigens / Q000032:analysis*; D045744:Cell Line, Tumor; D005260:Female; D005710:Gallium Radioisotopes; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D009842:Oligopeptides / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D005710:Gallium Radioisotopes; C526428:NGR peptide; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D018826:CD13 Antigens
keywords: CD13; CendR motif; NGR peptide; Neuropilin-1; iNGR peptide