Enabling translation of cancer cell proliferation PET imaging via droplet radiochemistry technology

PROJECT SUMMARY Despite the widespread use and success of [18F]FDG-PET imaging in oncology, there are many situations where [18F]FDG cannot be used for diagnosis or treatment monitoring, especially for cancers where there is high background uptake, low tissue density, or slow-growing tumors. Infection or inflammation frequently leads to

false positives. Many tracers are being developed that provide improved contrast, sensitivity, and accuracy compared to [18F]FDG. Of particular interest is the nucleoside analog [18F]FMAU, which is incorporated into DNA when tumor cells divide, thus directly measuring increased cell proliferation, a universal hallmark of cancer.

Promising clinical data of [11C]FMAU and preclinical data of [18F]FMAU have led to initial clinical studies of [18F]FMAU in cancer patients, and there is high interest in clinical studies of [18F]FMAU PET as a means to assess treatment response in diverse cancer types. However, the radiosynthesis of [18F]FMAU is very

challenging, hindering translational efforts such as multicenter clinical trials that are needed to ensure sufficient recruitment of patient populations. Over many years, Dr. Chen’s lab at USC has improved the [18F]FMAU synthesis using a 1-pot process, but it still involves lengthy reaction steps (~3 h synthesis), uses corrosive and

unstable reagents that are not compatible with automated synthesis modules, and has a relatively low activity yield (~5%), making adoption of this approach extremely difficult. To widely enable clinical studies, this proposal leverages an innovative droplet-radiochemistry approach developed in Dr. van Dam’s lab at UCLA, and now

being commercialized by DropletPharm, in which reactions are performed in 10 µL volumes instead of 1 mL volumes, enabling higher isotope concentration, higher reaction yields and much shorter synthesis time. A preliminary study showed [18F]FMAU could be produced in