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: Jamey P Weichert, Paul A Clark, Irawati K Kandela, Abram M Vaccaro, William Clarke, Marc A Longino, Anatoly N Pinchuk, Mohammed Farhoud, Kyle I Swanson, John M Floberg, Joseph Grudzinski, Benjamin Titz, Anne M Traynor, Hong-En Chen, Lance T Hall, Christopher J Pazoles, Perry J Pickhardt, John S Kuo
• Journal: Science translational medicine (Sci Transl Med) Vol. 6 Issue 240 Pg. 240ra75 (Jun 11 2014) ISSN: 1946-6242 [Electronic] United States
• PMID: 24920661 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Association for the Advancement of Science.

Chemical References

• Antineoplastic Agents
• Phosphorylcholine

Topics

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