title: Imaging of human pancreatic cancer xenografts by single-photon emission computed tomography with99mTc-Hynic-PEG-AE105.
abstract: The elevated expression of urokinase-type plasminogen activator receptor (uPAR) is associated with the poor prognosis of pancreatic cancer patients. Thus, uPAR is a promising candidate as a molecular target for the non-invasive imaging of pancreatic cancer. The present study aimed to develop a technetium-99m (99mTc)-labeled uPAR-binding peptide for non-invasive single-photon emission computed tomography (SPECT) assessment of uPAR expression in pancreatic cancer xenograft models. A linear high-affinity uPAR peptide antagonist, Hynic-PEG-AE105, was labeled with99mTc. Human uPAR-positive pancreatic cancer BxPC-3 cells were inoculated into nude mice. SPECT was performed in the pancreatic cancer xenograft mice models. The results showed that the rate of the99mTc labeling of Hynic-PEG-AE105 was 97.72±1.73%. The tumor uptake of99mTc-Hynic-PEG-AE105 was higher than the control inactive peptide99mTc-Hynic-PEG-AE105mut at 4 h (3.37±0.11 vs. 1.36±0.18; P<0.001) and 6 h (3.64±0.25 vs. 1.28±0.20; P<0.001) (n=10). Moreover, a significant correlation was observed between the tumor uptake of99mTc-Hynic-PEG-AE105 and uPAR expression (r=0.791, P=0.006). In conclusion, in the present study, a peptide-based SPECT tracer,99mTc-Hynic-PEG-AE105, with a high purity and specific radioactivity was synthesized.99mTc-Hynic-PEG-AE105 is a promising agent for the non-invasive determination of uPAR expression in pancreatic cancer.
authors.affiliation: Department of Nuclear Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Affiliated Hospital, Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China ; Department of General Surgery, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Y E
authors.initials: YE
authors.lastname: Tian
authors.affiliation: Department of Nuclear Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Nuclear Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Nuclear Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of General Surgery, First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Tan
keywords: integrin; pancreatic cancer; single-photon emission computed tomography; urokinase-type plasminogen activator receptor