In Vivo Imaging for the Detection and Quantitation of Transplanted Stem/Progenitor Cells in Nonhuman Primates
Tools and Technologies I
Statement of Benefit to California:
This proposal is focused on the optimization of small animal positron emission tomography (microPET) for in vivo tracking of transplanted human stem and progenitor cells in non-human primates. With this technology, cells are labeled by radioimmunoconjugates detectable via PET. The microPET scanner has previously been used to detect moderate levels of radiolabel successfully and the applicant proposes to optimize the technique for detection of extremely low label levels. The applicant proposes that these improvements may allow the labeling of stem and progenitor cells without affecting viability or function. The proposal’s first aim focuses on improving the sensitivity of the scanning technology by adjusting a wide array of technical parameters to support both cell identification and quantification. The second aim is to improve the methods of radiolabeling cells by testing new labels and optimizing radioactivity levels and incubation times. If successful, this proposal would enhance the sensitivity of PET imaging of transplanted cells while reducing the amount of radioactivity required. The reviewers agreed that this proposal addresses an important roadblock in stem cell research (ability to track transplanted cells) and would have broad applications if successful. They were enthusiastic about the technical aspects of the proposal, the preliminary data and the PI’s track record. They did raise some concerns about feasibility but expressed confidence in the assembled research team. The reviewers appreciated the potentially broad impact of this proposal. Development of sensitive, non-invasive, in vivo imaging of transplanted stem cells is a major roadblock to clinical stem cell therapy. The optimization of microPET technology proposed in this application would benefit preclinical research but could also lead to translatable improvements in human PET. One reviewer wondered why the technical experiments described in the first aim haven’t been done before, as they would clearly benefit many types of PET research. The reviewers commented that this is a well-designed research plan with clearly defined aims and milestones. Two reviewers raised questions about feasibility, specifically whether the applicant would achieve great enough sensitivity to detect cells that might migrate away from the injection site. One reviewer noted the high level of radiolabel required for detection by microPET in preliminary data and wondered if this could be lowered enough to ensure functional integrity of the labeled cells. However, the preliminary data included in the application was sufficient to persuade the reviewers that the research plan is indeed feasible, if ambitious. The reviewers were unanimous in their praise of the research team. They noted that the applicant has a strong track record in the field and has assembled a well-coordinated, interdisciplinary team. One reviewer commented that if this project can be done, this is the team to do it. It was noted that the applicant is funded by both the NIH and CIRM for related activities, but noted no overlap of budget or research effort. Overall, this is a strong, well-written proposal from a highly qualified research team with the potential for broad impact in the field.