Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy

Sci Transl Med. 2014 Jun 11;6(240):240ra75. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Female
  • Humans
  • Mice
  • Neoplasms / diagnosis*
  • Neoplasms / drug therapy*
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / therapeutic use*
  • Positron-Emission Tomography / methods
  • Tomography, Emission-Computed, Single-Photon / methods
  • Tomography, X-Ray Computed / methods
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Phosphorylcholine