Tools and Technologies I
Statement of Benefit to California:
This proposal aims to develop a wide diversity of novel probes for positron emission tomography (PET) imaging that allow for in vivo imaging of cell-based therapies in regenerative medicine and oncology that are translatable from animal models to patients. The technology development focuses on three themes that involve the design of small molecule PET probes, antibody-based PET probes, and novel reporter genes optimized for clinical monitoring of transplanted cells. The ability to track the distribution, engraftment, and proliferation of transplanted stem cell-derived populations is of considerable importance in the field and thus reviewers agreed that the potential impact of this proposal is significant. The design strategy was considered well conceived and each aim allows for clinical research studies. The PI has assembled a remarkable and large team in order to deliver milestones within a 2-year period. Overall, reviewers thought that the proposed milestones are logical and well described. The PI has assembled a large team and the preliminary data suggest that all aims can be completed. One reviewer felt that the principal drawback to this proposal is the need to more fully address potential pitfalls specifically related to use of the probes in stem cell populations, and use of the stem cells in immune-competent recipients. Most of the studies outlined in the proposal are focused on tracking immune T cell populations in hosts that may be immunocompromised. The immediate and direct applicability of this technology to embryonic stem cells or iPS cells, for example, was unclear since specific studies addressing translation of the technology to stem cell populations were not proposed. Reviewers were nevertheless excited about the development of this technology that if applied to stem cells would be valuable. Reviewers felt that the PI is very accomplished and well qualified for this project and has assembled a strong team. The PI also has outstanding support and equipment. The team has a proven track record with high likelihood of being able to accomplish the stated objectives. The ability to effectively track transplanted cell populations in vivo is a key issue that needs to be addressed to move cell therapies forward. Although this proposal utilizes hematopoietic cells as the primary subject for developing the probe technology, reviewers felt that the strengths in research design, approach, and PI’s experience would lead to a valuable and broadly applicable set of tools for stem cell research.