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: Boronated prodrugs have been developed that are particularly advantageous for use in boron proton capture therapy (BPCT) and boron neutron capture therapy (BNCT). Cancer-targeting moieties, such as heptamethine cyanine dyes (HMCDs), are linked to compounds including a plurality of boron isotopes, e.g., carboranes such as 1-amino-1-carbadodecaborate. Compounds of the present disclosure were demonstrated to deliver eleven boron-11 atoms per dye molecule selectively to breast cancer cells. Upon irradiation with proton or neutron beams and subsequent nuclear fusion reaction by proton capture, unstable 12C is generated in place of 11B, which is short lived and releases high energy alpha particles. There particles travel only a short distance within cell and/or a very close tumor microenvironment, damaging cellular DNA ultimately resulting in killing cancer cells, and are particularly useful with young patients and with deep tissue tumors located in critical organs which are difficult to remove by surgery.

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 provides for heptamethine cyanine dyes that possess both nuclear and near-infrared imaging capabilities. These dyes can be used for imaging, targeting and detecting tumors in patients.

Abstract: The present application provides compositions and methods for imaging traumatic brain injury using PET. The present application discloses using PET ligands targeting infiltrating neutrophils, such as a ligand of FPR, is useful for imaging inflammation. In one aspect, the ligand and imaging agent cFLFLF-PEG-64Cu.

Abstract: The present invention provides for heptamethine cyanine dyes that possess both nuclear and near-infrared imaging capabilities. These dyes can be used for imaging, targeting and detecting tumors in patients.

Abstract: The present application discloses a new multivalent peptide ligand specifically targeting polymorphonuclear leukocytes (PMNs) with favorable pharmacological parameters to monitor sites of inflammation for imaging. The detailed synthesis, characterization, and pharmacological evaluation of the ligands are reported here. Two separate peptide binding ligands for formyl peptide and tuftsin receptors were chosen to link together based on the high expression levels of the two receptors on activated PMNs The heterobivalency and pegylated links were incorporated in the structural design to improve the sensitivity of the detection and to improve the bioavailability along with blood clearance profile, respectively. Two chemical constructs: cFLFLF-(PEG)n-TKPPR-99mTc (n=4, 12) were evaluated in vitro with human PMNs for binding affinity and bioavailability. As a result, FLFLF-(PEG)12-TKPPR99mTc was found to have more favorable pharmacological properties and was therefore used for further in vivo studies.