High throughput design, synthesis and in vivo evaluation of targeted molecular imaging agents. This is a 3-year proposal in response to the RFA-OD-10-005. This proposal addresses components of all 5 thematic areas with the closest association with the thematic area """"""""Applying Genomics and other High throughput technologies"""""""". Molecular imaging, a noninvasive, quantitative visualization of in vivo molecular processes occurring at the cellular and sub cellular level is becoming an enabling technology for personalized medicine. Development of target specific molecular imaging agents is critical for the growth of this field. Current limitations for the rapid development of targeted molecular imaging agents include the complex design, synthesis and screening approaches for radiolabeled compounds, the short half-lives of the radiolabeled compounds, automation of the synthesis of radiolabeled compounds, rapid in vivo screening of the compounds and finally rapid automated analysis of the large data sets acquired. We are therefore proposing to address these limitations by developing a high-throughput platform that will streamline not only the in vitro selection but also the synthesis and in vivo evaluation of novel targeted molecular imaging agents. We will utilize the advances made in combinatorial chemistry, microfabrication, microfluidics and small animal imaging technologies to screen peptide based libraries designed as targeted molecular imaging agents for utilization with PET. We have assembled a multidisciplinary team of investigators Professors Sutcliffe (radiochemist), Cherry (PET physicist), Revzin (chemical engineer) and Qi (physicist/mathematician). In line with the purpose of the Recovery Act we are requesting funds for students and post doctoral fellows to support training in the field as well as technician support for Dave Kukis and Jennifer Fung (staff at CMGI) to enable job preservation. We believe that by focusing our efforts on high-throughput compound retrieval and in vivo screening our approach has the potential to minimize the need for extensive and time consuming in vitro analysis These advances in the development of molecular probes as targeted imaging biomarkers will significantly help to facilitate personalized medicine, improving our ability to detect, diagnose, stage, monitor and guide treatment response and determine prognosis in many diseases.

Public Health Relevance

Molecular imaging is a noninvasive, quantitative visualization of in vivo molecular processes occurring at the cellular and sub cellular level that is becoming an enabling technology for personalized medicine. We are proposing to accelerate the development of target specific molecular imaging agents. These advances in the development of molecular imaging agents as targeted imaging biomarkers will significantly help to facilitate personalized medicine, improving our ability to detect, diagnose, stage, monitor and guide treatment response and determine prognosis in many diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
High Impact Research and Research Infrastructure Programs—Multi-Yr Funding (RC4)
Project #
1RC4EB012836-01
Application #
8047904
Study Section
Special Emphasis Panel (ZRG1-MOSS-G (55))
Program Officer
Conroy, Richard
Project Start
2010-09-30
Project End
2013-09-29
Budget Start
2010-09-30
Budget End
2013-09-29
Support Year
1
Fiscal Year
2010
Total Cost
$3,519,967
Indirect Cost
Name
University of California Davis
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Shin, Dong-Sik; You, Jungmok; Rahimian, Ali et al. (2014) Photodegradable hydrogels for capture, detection, and release of live cells. Angew Chem Int Ed Engl 53:8221-4
Wang, Guobao; Qi, Jinyi (2013) Direct estimation of kinetic parametric images for dynamic PET. Theranostics 3:802-15
Siltanen, Christian; Shin, Dong-Sik; Sutcliffe, Julie et al. (2013) Micropatterned photodegradable hydrogels for the sorting of microbeads and cells. Angew Chem Int Ed Engl 52:9224-8
Rahmim, Arman; Qi, Jinyi; Sossi, Vesna (2013) Resolution modeling in PET imaging: theory, practice, benefits, and pitfalls. Med Phys 40:064301
Boucher, David L; Chen, Jane Qian; Cherry, Simon R et al. (2012) Establishment of clonal MIN-O transplant lines for molecular imaging via lentiviral transduction & in vitro culture. PLoS One 7:e39350
Wang, Guobao; Qi, Jinyi (2012) An optimization transfer algorithm for nonlinear parametric image reconstruction from dynamic PET data. IEEE Trans Med Imaging 31:1977-88
Shin, Dong-Sik; Seo, Jeong Hyun; Sutcliffe, Julie L et al. (2011) Photolabile micropatterned surfaces for cell capture and release. Chem Commun (Camb) 47:11942-4
Cheng-Liao, Jinxiu; Qi, Jinyi (2011) PET image reconstruction with anatomical edge guided level set prior. Phys Med Biol 56:6899-918