1. Alkylphosphocholine Analogs for Broad-Spectrum Cancer Imaging and Therapy
- Author
-
John S. Kuo, Mohammed Farhoud, Jamey P. Weichert, Benjamin Titz, Perry J. Pickhardt, Kyle I. Swanson, Paul A. Clark, Christopher J. Pazoles, Irawati Kandela, Abram M. Vaccaro, John M. Floberg, Anne M. Traynor, Anatoly Pinchuk, Joseph Grudzinski, Lance T. Hall, William T. Clarke, Marc Longino, and Hong En Chen
- Subjects
Phosphorylcholine ,Antineoplastic Agents ,Alkylphosphocholine ,Cancer imaging ,Article ,Mice ,chemistry.chemical_compound ,In vivo ,Cancer stem cell ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Humans ,Tomography, Emission-Computed, Single-Photon ,medicine.diagnostic_test ,business.industry ,General Medicine ,Xenograft Model Antitumor Assays ,chemistry ,Positron emission tomography ,Cell culture ,Positron-Emission Tomography ,Female ,Tomography ,Tomography, X-Ray Computed ,business ,Nuclear medicine ,Emission computed tomography - 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.
- Published
- 2014
- Full Text
- View/download PDF