title: Synthesis and evaluation of a68Ga-labeled bradykinin B1 receptor agonist for imaging with positron emission tomography.
abstract: A novel68Ga-labeled bradykinin B1 receptor (B1R) agonist,68Ga-Z01115, was synthesized and evaluated for imaging with positron emission tomography (PET). Z01115 exhibited good binding affinity (Ki=25.4±5.1nM) to hB1R.68Ga-Z01115 was prepared in 74±5 decay-corrected radiochemical yield with >99% radiochemical purity and 155±89GBq/µmol (4.2±2.4Ci/μmol) specific activity.68Ga-Z01115 was stable in vitro in mouse plasma (93% remaining intact after 60min incubation), and relatively stable in vivo (51±5% remaining intact at 5min post-injection). PET imaging and biodistribution studies in mice showed that68Ga-Z01115 cleared rapidly from nontarget tissues/organs, and generated high target-to-nontarget contrast images. The uptake of68Ga-Z01115 in B1R-positive (B1R+) tumor was 5.65±0.59%ID/g at 1h post-injection. Average contrast ratios of B1R+ tumor-to-B1R- tumor, -to-blood and -to-muscle were 24.3, 24.4 and 82.9, respectively. Uptake of68Ga-Z01115 in B1R+ tumors was reduced by ∼90% with co-injection of cold standard, confirming it was mediated by B1R. Our data suggest that68Ga-Z01115 is a promising tracer for imaging the expression of B1R that is overexpressed in a variety of cancers.
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Amouroux
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Jinhe
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Silvia
authors.initials: S
authors.lastname: Jenni
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Navjit
authors.initials: N
authors.lastname: Hundal-Jabal
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Nadine
authors.initials: N
authors.lastname: Colpo
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Jutta
authors.initials: J
authors.lastname: Zeisler
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada; Department of Radiology, University of British Columbia, 3350-950 West 10th Avenue, Vancouver, British Columbia V5Z 4E3, Canada. Electronic address: klin@bccrc.ca.
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada; Department of Radiology, University of British Columbia, 3350-950 West 10th Avenue, Vancouver, British Columbia V5Z 4E3, Canada. Electronic address: fbenard@bccrc.ca.
authors.forename: François
authors.initials: F
authors.lastname: Bénard
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005710:Gallium Radioisotopes; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D009942:Organometallic Compounds / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry; D049268:Positron-Emission Tomography; D043783:Receptor, Bradykinin B1 / Q000819:agonists*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: C000621779:68Ga-Z01115; D005710:Gallium Radioisotopes; D009942:Organometallic Compounds; D043783:Receptor, Bradykinin B1
keywords: Agonist; Antagonist; Bradykinin B1 receptor; Gallium-68; Positron emission tomography