title: Peptide targeted high-resolution molecular imaging of prostate cancer with MRI.
abstract: Non-invasive accurate detection of prostate cancer is critical for clinical management of the disease. Molecular MRI has a potential for accurate detection of prostate cancer with high spatial resolution. Fibronectin is a hallmark of epithelial-mesenchymal transition occurred in aggressive prostate cancer and highly expressed in malignant tumors. A pentapeptide CREKA targeted contrast agent CREKA-dL-(DOTA-Gd)4 was synthesized and evaluated to target fibrin-fibronectin complexes in tumor extracellular matrix for molecular MRI of prostate cancer. The contrast agent was synthesized by solid-phase peptide synthesis. The T1 relaxivity of CREKA-(DOTA-Gd)4 at 1.5 T was 33.2 mM(-1)s(-1) per molecule (8.3 per Gd). The fluorescence imaging showed that CREKA specifically bound to orthotopic PC3 prostate tumor in athymic nude mice. Strong enhancement was observed in the tumor tissue injected with CREKA-(DOTA-Gd)4 in the first 5 minutes post-injection before MR signal became visible in the bladder at a low dose of 0.03 mmol-Gd/kg. The targeted contrast agent exhibited minimal Gd retention in the main organs and tissues 2 days after injection. The peptide targeted contrast agent CREKA-(DOTA-Gd)4 is promising for high-resolution molecular MRI of prostate cancer.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Cleveland, Ohio 44106, USA.
authors.forename: Xueming
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Cleveland, Ohio 44106, USA.
authors.forename: Guanping
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Translational Hematology & Oncology Research, Cleveland Clinic Cleveland, Ohio 44195, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindner
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University Cleveland, Ohio, USA.
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
authors.affiliation: Provincial Key Lab of Fine Chemistry, Hainan University Haikou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Cleveland, Ohio 44106, USA.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
keywords: MRI; Molecular imaging; peptide; prostate cancer; targeted contrast agent