Breast Cancer (BC) is the leading cause of cancer death for woman in the US. Breast cancer is treated by a combination of surgery, radiation, and various types of chemo and targeted therapeutic strategies. Approximately half of patients who have positive sentinel lymph nodes at surgery (and as many as 25% of patients who do not) eventually present with metastatic disease. Over 70% of BC patients eventually have skeletal involvement making bone the single most prevalent site of metastasis in BC. BioVinc has developed a novel bisphosphonate-tagged PET imaging strategy which we have shown to more thoroughly image bone disease including earlier bone effects of disease than current PET probes of other diagnostic tools. In this STTR R41 application we propose 2nd generation 18F-BP-PET imaging probes to provide breast cancer patients, a more sensitive measure of bone metastases prompting them to take advantage of new treatment strategies known to improve survival in this group. It is our goal to show that these innovative BP-PET probes can overcome some of the disadvantages of current imaging strategies for BC and provide earlier diagnosis of the bone metastases. Our innovative chemistry design offers rapid preparation (within one 18F half-life) of the proposed PET probes. Cold chemistry will be performed at the BioVinc laboratories by Dr. Frank Ebetino and the team, and then elaborated for radiochemistry requirements together with Drs. Kai Chen and Charles McKennaâs group at USC. All radiochemistry, including in situ cyclotron generation of the radioisotope 18F, as well as the in vivo animal studies and PET imaging will be performed under Dr. Kai Chenâs direction at the USC Molecular Imaging Center. We will use 18F-NaF probes as a control imaging agent in an orthotopic rodent model of breast cancer which reliably results in related bone metastases and compare them with our best novel probe for the detection of early changes in the bone due to disease. These proof of concept studies will position our research for rapid translational development in a subsequent Phase II STTR program.
Public Health Relevance Statement: PROJECT NARRATIVE Bone metastases is a serious potential side effect stemming from breast cancer and leads to serious skeletal related events including severe pain and fractures. There is a serious unmet medical need for improved methods to promptly identify and manage therapy for this complication. A novel PET imaging probe to more accurately identify skeletal metastases will be developed and thereby reduce patient morbidity and mortality.
Project Terms: analog; Animal Cancer Model; Animals; base; bisphosphonate; bone; Bone Diseases; bone imaging; Bone neoplasms; Bone Resorption; bone turnover; Brain; Breast cancer metastasis; Breast Cancer Model; Breast Cancer Patient; Cancer Diagnostics; Cancer Etiology; Cessation of life; Characteristics; Chemistry; Clinical; Collaborations; Complex; Complication; Consult; Cyclotrons; Data Analyses; design; Detection; Development; Diagnosis; Diagnostic; Diagnostic radiologic examination; Disadvantaged; Disease; Disease Progression; Dose; Early Diagnosis; Early treatment; Flare; Fracture; Generations; Goals; Half-Life; Healthcare Systems; Human; Image; imaging agent; imaging modality; imaging probe; improved; In Situ; in vivo; innovation; Investigation; Label; Laboratories; Lesion; Letters; Liver; Lung; Magnetic Resonance Imaging; malignant breast neoplasm; Measures; Medical; Medical Imaging; Metastatic Neoplasm to the Bone; Methods; Modeling; molecular imaging; Molecular Weight; Morbidity - disease rate; mortality; Mus; Neoplasm Metastasis; novel; Operative Surgical Procedures; Osteolytic; Pain; patient population; patient subsets; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Physicians; Positioning Attribute; Positron-Emission Tomography; Preparation; programs; Quality of life; Radiation; radiochemical; Radiochemistry; Radioisotopes; Recording of previous events; Research; Research Personnel; Resources; Rheumatoid Arthritis; Rodent Model; Safety; safety study; Sentinel Lymph Node; side effect; single photon emission computed tomography; Site; skeletal; skeletal-related events; Skeleton; Small Business Technology Transfer Research; small molecule; Specificity; stem; success; targeted treatment; Testing; Therapeutic; Time; tool; treatment response; treatment strategy; Visceral; Wo
