Dataset Information

Integrin ?6-Targeted Positron Emission Tomography Imaging of Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin ?6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin ?6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, 18F-RWY, based on this integrin ?6-targeted RWY peptide for positron emission tomography (PET) imaging of CRC. Integrin ?6 was overexpressed on several CRC cells including HT29 cells where the biotin-labeled RWY peptide colocalized with integrin ?6. 18F-RWY PET imaging was performed on subcutaneous, chemically induced, and genetically engineered CRC mice. 18F-RWY generated high PET signals in subcutaneous HT29 tumors, and the tumor uptake of 18F-RWY was reduced by a blocking study using nonradio-labeled RWY. Moreover, 18F-RWY PET imaging enabled detection of CRC in chemically induced and genetically engineered CRC mice. The overexpression of integrin ?6 in tumor tissues isolated from chemically induced and genetically engineered CRC mice was confirmed. These results demonstrate the potential clinical application of 18F-RWY for PET imaging of CRC.

SUBMITTER: Xiao YT

PROVIDER: S-EPMC6761804 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrin α6-Targeted Positron Emission Tomography Imaging of Colorectal Cancer.

Xiao Yi-Tai YT Zhou Chao C Ye Jia-Cong JC Yang Xiao-Chun XC Li Zhi-Jian ZJ Zheng Xiao-Bin XB Mei Yan Y Li Xin-Ling XL Zhang Wei-Guang WG Fan Wei W Zeng Mu-Sheng MS Li Jian-Jun JJ Feng Guo-Kai GK

ACS omega 20190911 13

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin α6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin α6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, <sup>18</sup>F-RWY, based on this integrin α6-targete ...[more]

PMID: 31572857

Similar Datasets

Project description:UnlabelledThe recent advancement of nanotechnology has provided unprecedented opportunities for the development of nanoparticle enabled technologies for detecting and treating cancer. Here, we reported the construction of a PET trackable organic nanoplatform based on phage particle for targeted tumor imaging.MethodThe integrin ?(v)?(3) targeted phage nanoparticle was constructed by expressing RGD peptides on its surface. The target binding affinity of this engineered phage particle was evaluated in vitro. A bifunctional chelator (BFC) 1,4,7,10-tetraazadodecane-N,N',N",N"'-tetraacetic acid (DOTA) or 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo [6.6.6] icosane-1-ylamino) methyl) benzoic acid (AmBaSar) was then conjugated to the phage surface for (64)Cu(2+) chelation. After (64)Cu radiolabeling, microPET imaging was performed in U87MG tumor model and the receptor specificity was confirmed by blocking experiments.ResultsThe phage-RGD demonstrated target specificity based on ELISA experiment. According to the TEM images, the morphology of the phage was unchanged after the modification with BFCs. The labeling yield was 25 ± 4% for (64)Cu-DOTA-phage-RGD and 46 ± 5% for (64)Cu-AmBaSar-phage-RGD, respectively. At 1 h time point, (64)Cu-DOTA-phage-RGD and (64)Cu-AmBaSar-phage-RGD have comparable tumor uptake (~ 8%ID/g). However, (64)Cu-AmBaSar-phage-RGD showed significantly higher tumor uptake (13.2 ± 1.5 %ID/g, P<0.05) at late time points compared with (64)Cu-DOTA-phage-RGD (10 ± 1.2 %ID/g). (64)Cu-AmBaSar-phage-RGD also demonstrated significantly lower liver uptake, which could be attributed to the stability difference between these chelators. There is no significant difference between two tracers regarding the uptake in kidney and muscle at all time points tested. In order to confirm the receptor specificity, blocking experiment was performed. In the RGD blocking experiment, the cold RGD peptide was injected 2 min before the administration of (64)Cu-AmBaSar-phage-RGD. Tumor uptake was partially blocked at 1 h time point. Phage-RGD particle was also used as the competitive ligand. In this case, the tumor uptake was significantly reduced and the value was kept at low level consistently.ConclusionIn this report, we constructed a PET trackable nanoplatform based on phage particle and demonstrated the imaging capability of these targeted agents. We also demonstrated that the choice of chelator could have significant impact on imaging results of nano-agents. The method established in this research may be applicable to other receptor/ligand systems for theranostic agent construction, which could have an immediate and profound impact on the field of imaging/therapy and lay the foundation for the construction of next generation cancer specific theranostic agents.

Dataset Information

Integrin ?6-Targeted Positron Emission Tomography Imaging of Colorectal Cancer.

Publications

Integrin α6-Targeted Positron Emission Tomography Imaging of Colorectal Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets