Alkylphosphocholine Analogs for Broad Spectrum Cancer Imaging and Therapy

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Weichert et al.
Many solid tumors contain an over-abundance 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 PET imaging (124I) or molecular radiotherapeutic (131I) agent. CLR1404 analogs displayed prolonged tumor-selective retention in 55 in vivo rodent and human cancer and cancer stem cell models. 131I-CLR1404 also displayed efficacy (tumor growth suppression, survival extension) in a wide range of human tumor xenograft models. Human PET/CT and SPECT/CT imaging in advanced cancer patients with 124I- or 131I-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 124I-CLR1404 tumor imaging for planning 131I-CLR1404 therapy.