title: Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer.
abstract: Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients.
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) and Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences , Wuhan 430071, China.|Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California94305, United States.
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California94305, United States.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California94305, United States.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California94305, United States.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California94305, United States.
authors.forename: Mathias
authors.initials: M
authors.lastname: Loft
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) and Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences , Wuhan 430071, China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Ding
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California94305, United States.
authors.forename: Changhao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California94305, United States.
authors.forename: Liying
authors.initials: L
authors.lastname: Xu
authors.affiliation: Chinese Academy of Medical Science, Peking Union Medical College Hospital , Department of Ultrasound, Beijing, 100730, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Chinese Academy of Medical Science, Peking Union Medical College Hospital , Department of Ultrasound, Beijing, 100730, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Chinese Academy of Medical Science , Institute of Radiation Medicine, Department of Molecular Nuclear Medicine, Tianjin, 300192, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) and Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences , Wuhan 430071, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California94305, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) and Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences , Wuhan 430071, China.
authors.forename: Xuechuan
authors.initials: X
authors.lastname: Hong
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D004355:Drug Stability; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D051379:Mice; D000442:Octanols / Q000737:chemistry; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D018004:Receptors, Bombesin / Q000378:metabolism*; D014018:Tissue Distribution; D014867:Water / Q000737:chemistry
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D000442:Octanols; D018004:Receptors, Bombesin; D014867:Water