title: Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy.
abstract: Many solid tumors contain an overabundance of phospholipid ethers relative to normal cells. Capitalizing on this difference, we created cancer-targeted alkylphosphocholine (APC) analogs through structure-activity analyses. Depending on the iodine isotope used, radioiodinated APC analog CLR1404 was used as either a positron emission tomography (PET) imaging ((124)I) or molecular radiotherapeutic ((131)I) agent. CLR1404 analogs displayed prolonged tumor-selective retention in 55 in vivo rodent and human cancer and cancer stem cell models. (131)I-CLR1404 also displayed efficacy (tumor growth suppression and survival extension) in a wide range of human tumor xenograft models. Human PET/CT (computed tomography) and SPECT (single-photon emission computed tomography)/CT imaging in advanced-cancer patients with (124)I-CLR1404 or (131)I-CLR1404, respectively, demonstrated selective uptake and prolonged retention in both primary and metastatic malignant tumors. Combined application of these chemically identical APC-based radioisosteres will enable personalized dual modality cancer therapy of using molecular (124)I-CLR1404 tumor imaging for planning (131)I-CLR1404 therapy.
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA. jweichert@uwhealth.org j.kuo@neurosurgery.wisc.edu.
authors.forename: Jamey P
authors.initials: JP
authors.lastname: Weichert
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Clark
authors.affiliation: Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
authors.forename: Irawati K
authors.initials: IK
authors.lastname: Kandela
authors.affiliation: Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
authors.forename: Abram M
authors.initials: AM
authors.lastname: Vaccaro
authors.affiliation: Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
authors.forename: William
authors.initials: W
authors.lastname: Clarke
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Longino
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Pinchuk
authors.affiliation: Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Farhoud
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Kyle I
authors.initials: KI
authors.lastname: Swanson
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Floberg
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Grudzinski
authors.affiliation: Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Titz
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.affiliation: Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Hong-En
authors.initials: HE
authors.lastname: Chen
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Lance T
authors.initials: LT
authors.lastname: Hall
authors.affiliation: Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pazoles
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Perry J
authors.initials: PJ
authors.lastname: Pickhardt
authors.affiliation: Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. jweichert@uwhealth.org j.kuo@neurosurgery.wisc.edu.
authors.forename: John S
authors.initials: JS
authors.lastname: Kuo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D049268:Positron-Emission Tomography / Q000379:methods; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010767:Phosphorylcholine