title: Radiogallium Complex-Conjugated Bifunctional Peptides for Detecting Primary Cancer and Bone Metastases Simultaneously.
abstract: (68)Ga (T(1/2) = 68 min, a generator-produced nuclide) is an interesting radionuclide for clinical positron emission tomography (PET). Recently, it was reported that radiogallium-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated (Asp)n peptide [Ga-DOTA-(Asp)n] has great potential for bone metastases imaging. In the current study, a compound containing an aspartic acid peptide linker (D11) as a carrier to bone metastases, an RGD peptide [c(RGDfK) peptide] as a carrier to the primary cancer, and Ga-DOTA as a stable radiometal complex for imaging in one molecule, Ga-DOTA-D11-c(RGDfK), was designed, prepared, and evaluated to detect both the primary cancer and bone metastases simultaneously using (67)Ga, which is easy to handle. After DOTA-D11-c(RGDfK) was synthesized using Fmoc-based solid-phase methodology, (67)Ga-DOTA-D11-c(RGDfK) was prepared by complexing DOTA-D11-c(RGDfK) with (67)Ga. Hydroxyapatite binding assays, integrin binding assays, biodistribution experiments, and single photon emission tomography (SPECT) imaging using tumor-bearing mice were performed using (67)Ga-DOTA-D11-c(RGDfK). (67)Ga-DOTA-D11-c(RGDfK) was prepared with a radiochemical purity of >97%. In vitro, (67)Ga-DOTA-D11-c(RGDfK) had a high affinity for hydroxyapatite and αvβ3 integrin. In vivo, (67)Ga-DOTA-D11-c(RGDfK) exhibited high uptake in bone and tumor. The accumulation of (67)Ga-DOTA-D11-c(RGDfK) in tumor decreased when it was co-injected with c(RGDfK) peptide. (68)Ga-DOTA-D11-c(RGDfK) has great potential as a PET tracer for the diagnosis of both the primary cancer and bone metastases simultaneously.
authors.affiliation: †Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.|‡Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: †Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: †Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishizaki
authors.affiliation: †Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokokawa
authors.affiliation: †Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: §Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: §Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
authors.affiliation: †Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Odani
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D005260:Female; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D005710:Gallium Radioisotopes; D039302:Integrin alphaVbeta3; D010446:Peptide Fragments; D019275:Radiopharmaceuticals