2. Academic Validation
  3. Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy

Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy

  • Sci Transl Med. 2014 Jun 11;6(240):240ra75. doi: 10.1126/scitranslmed.3007646.
Jamey P Weichert 1,  Paul A Clark 2,  Irawati K Kandela 3,  Abram M Vaccaro 3,  William Clarke 3,  Marc A Longino 4,  Anatoly N Pinchuk 4,  Mohammed Farhoud 5,  Kyle I Swanson 2,  John M Floberg 6,  Joseph Grudzinski 7,  Benjamin Titz 3,  Anne M Traynor 8,  Hong-En Chen 2,  Lance T Hall 9,  Christopher J Pazoles 3,  Perry J Pickhardt 9,  John S Kuo 10
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 3 Cellectar Biosciences Inc., 3301 Agriculture Drive, Madison, WI 53716, USA.
  • 4 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.
  • 5 Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 6 Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 7 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.
  • 8 Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 9 Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
  • 10 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.
PMID: 24920661 DOI: 10.1126/scitranslmed.3007646
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.

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