Radiolabeled Cyclosaligenyl Monophosphates of 5-Iodo-2′-deoxyuridine, 5-Iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-Fluorothymidine for Molecular Radiotherapy of Cancer: Synthesis and Biological Evaluation

• DOI: 10.1021/jm201482p
• Publication Date: 2012-02-16T17:23:30Z
• Authors: Zbigniew P. Korty...; Yu Kimura; Kotaro Inoue; Elizabeth Mack; Janina Baranowska...
• Keywords: Ovarian Neoplasms; Cell Survival; Hydrolysis; Stereoisomerism; 3. Good health; Iodine Radioisotopes; Structure-Activity Relationship; 03 medical and health sciences; 0302 clinical medicine; Butyrylcholinesterase; Cell Line, Tumor; Neoplasms; Thymidine Monophosphate; Humans; Female; Cholinesterase Inhibitors; Molecular Targeted Therapy; Drug Screening Assays, Antitumor; Radiopharmaceuticals; Colorectal Neoplasms; Glioblastoma; Radionuclide Imaging; Uridine Monophosphate

Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed deliver lethal doses radiation cells. These compounds can be radiolabeled SPECT- and PET-compatible radionuclides as well suitable for Auger electron therapies. This characteristic provides an avenue the personalized comprehensive treatment strategy that comprises diagnostic imaging identify sites disease, followed by targeted based on results. The developed radiosynthetic methods produce no-carrier-added products high radiochemical yield purity. interaction these their target, butyrylcholinesterase, depends stereochemistry around P atom. IC50 values nanomolar range. In vitro studies indicate delivered cell nucleus sufficient kill several difficult treat malignancies including glioblastoma ovarian colorectal cancers.