Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates generally to a class of 2-aminothiazole derivatives which have recently been identified as allosteric enhancers of the A1? adenosine receptor. These compounds, and therapeutic compositions containing them, are useful for treating conditions in which activation of the A1? adenosine receptor would be beneficial, for example, those conditions in which stimulation of angiogenesis would improve blood flow to ischemic tissues.

Abstract: The present invention provides methods for making a novel class of 1-deoxy paclitaxel derivatives. These derivatives include 1-deoxy paclitaxel. The derivatives of the present invention are potent cytotoxic agents.