PROTON ACTIVATED ATOMIC MEDICINE

• Main Authors: Pan, Dongfeng, Rich, Tyvin A, Chordia, Mahendra D
• Format: Patent
• Language: English
• Published: 28.01.2021
• Subjects: APPARATUS THEREFOR; CHEMISTRY; DERIVATIVES THEREOF; ELECTROTHERAPY; GENERAL METHODS OF ORGANIC CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MAGNETOTHERAPY; MEDICAL OR VETERINARY SCIENCE; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; RADIATION THERAPY; SUGARS; ULTRASOUND THERAPY

The present application provides compositions and methods for preparing and using "heavy" nucleotide derivatives of thymidine or uridine by replacing the oxygen atom attached to one or more of positions with non-radioactive oxygen-18 (18O), administering it to a subject to target a tumor including incorporation into tumor cell DNA, and then treating the tumor with proton beam therapy to transmutate the 18O to 18F, resulting in a break of the new fluorine-phosphorous bond. This chemical event destabilizes ribose-phosphate DNA back-bone and base pairing thus produce single- and double strand breaks, clusters lesions that can lead to irreparable DNA damage and enhanced tumor cell killing. The atomic, chemical, and physical aspects result in the use of lower radiation doses and significantly alter acute and late morbidity of radiotherapy. Heavy thymidine and heavy uridine derivatives labeled with 18O have been made and tested.