BLR&D Research Career Scientist Award Application

BLR

• 批准号: 10047241
• 负责人: TIMOTHY J. HOFFMAN
• 金额: --
• 依托单位: HARRY S. TRUMAN MEMORIAL VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10047241
• 关键词: Alpha Particles; Androgen Receptor; Androgens; Apoptosis; Area; Award; Bombesin; Bombesin Receptor; Cancer Patient; Cardiology; Cell Cycle; Cell Line; Cells; Cessation of life; Chemoresistance; Clinical; Clinical Oncology; Clinical Research; Clinical Trials; Collaborations; Cyclic GMP; DNA Repair; Data; Dependence; Development; Diagnosis; Diagnostic; Discipline of Nuclear Medicine; Disease; Drug Kinetics; Drug usage; Endotoxins; Evaluation; Funding; Goals; Growth; Guidelines; Human; ICAM1 gene; Image; In Vitro; Individual; Infrastructure; Investigation; Label; Laboratories; Magnetic Resonance Imaging; Malignant neoplasm of prostate; Maximum Tolerated Dose; Measures; Mentorship; Methods; Molecular Target; National Center for Research Resources; Neurosciences; Oncology; Optics; Organ; Patients; Peptides; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Positron; Positron-Emission Tomography; Preparation; Procedures; Production; Progressive Disease; Prostatic Neoplasms; Pyrogens; Quality Control; RNA Splicing; Radiation therapy; Radioisotopes; Radiolabeled; Radiometry; Radionuclide Generators; Radiopharmaceuticals; Radium-224; Regulation; Research; Research Activity; Research Personnel; Resistance; Running; Scientist; Series; Services; Sheep; Staging; Sterility; Targeted Radiotherapy; Technology; Therapeutic; Therapeutic Agents; Tissues; Toxic effect; Toxicology; Translating; Translations; Treatment Efficacy; United States; United States National Institutes of Health; Validation; Variant; Veterans; Xenograft Model; Xenograft procedure; abiraterone; advanced prostate cancer; androgen sensitive; base; bench to bedside; cancer cell; cancer diagnosis; cancer imaging; career; chemotherapy; cytotoxicity; docetaxel; dosimetry; drug development; drug discovery; efficacy evaluation; falls; imaging biomarker; in vivo; male; molecular imaging; novel; operation; pre-clinical; prevent; programs; prostate cancer cell line; protein expression; radiochemical; receptor; scale up; service utilization; single photon emission computed tomography; targeted delivery; targeted treatment; theranostics; translational research program

As a VA Research Career Scientist, Dr. Timothy J. Hoffman’s research activities span 5 distinct but interrelated areas involving translational drug development in oncology-predominantly related to molecular imaging and targeted radiotherapy. The primary research activity is currently focused on developing radiolabeled receptor targeted theranostic (diagnostic and therapeutic) drugs for use in diagnosing, staging, and treating advanced prostate cancer (PC). To achieve this programmatic goal, we are evaluating a combination of Ga-68 diagnostic positron emitting agents for use in clinical nuclear medicine PET imaging and Pb-212 alpha particle therapeutic agents for the systemic delivery of targeted radiotherapy to Bombesin (BB2) receptor positive prostate cancers. This bench to bedside program involves 1) basic radiochemical synthesis of novel radiopharmaceuticals, 2) In vitro evaluation of cytotoxicity using a panel of human prostate cancer cell lines representative of the spectrum of prostate cancer from androgen dependent to androgen independent as well as incorporating chemotherapy naïve and resistant cell lines, 3) In vivo investigation into the utility of these systemically administered theranostic agents to accurately target receptor positive cells permitting quantitative PET imaging for diagnosis and staging of the Ga-68 labeled agent, 4) Assessing the therapeutic efficacy of the Pb-212 labeled agent for treating human PC xenografts, and 5) Performing the necessary tissue dosimetry and toxicity studies to enable the filing of a Physician sponsored IND application to the FDA as one of the final steps toward translating these agents into clinical trials. The second focus of program activity involves establishing the Truman VA Clinical Research Radiopharmacy (CRR) through VA ShEEP-IC funding for the production of novel short lived PET radiopharmaceuticals to be utilized in clinical oncology and nuclear medicine research. The lack of research radiopharmacy infrastructure as a major roadblock preventing the translation of drug discoveries from the bench to the clinic. The CRR infrastructure and necessary hot cell shielding technology is currently being procured with a goal of having a fully operational CRR that is compliant with FDA, NRC, NHPP regulations and USP guidelines by the Fall of 2019. The third focus of program activity involves directing the operation of the VA Biomolecular Imaging Center which is operated as a shared core research service to provide preclinical molecular imaging services utilizing PET, SPECT, CT, 7T MRI, Optical, and Bioluminescent technologies to VA research investigators primarily in the areas of oncology, cardiology, and neuroscience. The fourth and fifth foci of program activity involves formal scientific collaboration and scientific mentorship of clinicians and basic scientists in the areas of oncology and molecular imaging on 4 active VA Merit awards, the new VA Open Field Blast Core, 1 VA CDA2 award, 1 NIH RO1 award, and 1 NCRR T32 award.

作为VA研究职业科学家，Timothy J. Hoffman博士的研究活动跨越5个不同的领域