title: An (125)I-labeled octavalent peptide fluorescent nanoprobe for tumor-homing imaging in vivo.
abstract: Targeting radiopeptides are promising agents for radio-theranostics. However, in vivo evaluation of their targeting specificity is often obscured by their short biologic half-lives and low binding affinities. Here, we report an approach to efficiently examine targeting radiopeptides with a new class of octavalent peptide fluorescent nanoprobe (Octa-FNP) platform, which is composed of candidate targeting peptides and a tetrameric far-red fluorescent protein (tfRFP) scaffold. To shed light on this process, (125)I-Octa-FNP, (125)I-tfRFP and (125)I-peptide were synthesized, and their targeting functionalities were compared. Both fluorescence imaging and radioactive quantification results confirmed that (125)I-Octa-FNP had a significantly higher cellular binding capability than (125)I-tfRFP. In vivo biodistribution studies show that at 6 h post-injection, (125)I-Octa-FNP had 2-fold and 30-fold higher tumor uptake than that of (125)I-tfRFP and (125)I-peptide, respectively. Moreover, γ-imaging at 24 h post-injection revealed a remarkable accumulation of (125)I-Octa-FNP in the tumor while maintaining an extremely low background contrast, which was further confirmed by immunofluorescence analysis. These data suggested that, as an engineered and multivalent platform, Octa-FNP could enhance the tumor targeting of a designed peptide and provide excellent contrast radioimaging, making it a valuable tool for the evaluation of the targeting ability of specifically designed radiopeptides for cancer theranostics.
authors.affiliation: Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Luo
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.forename: Honglin
authors.initials: H
authors.lastname: Jin
authors.forename: Di
authors.initials: D
authors.lastname: Fan
authors.forename: Lisen
authors.initials: L
authors.lastname: Lu
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D007457:Iodine Radioisotopes / Q000737:chemistry*; D008164:Luminescent Proteins / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods; D000097573:Red Fluorescent Protein
chemical_list: D007457:Iodine Radioisotopes; D008164:Luminescent Proteins; D010455:Peptides; D000097573:Red Fluorescent Protein