UC San Diego

Cancer is responsible for over 8 million deaths annually and the number of new cases is expected to increase by approximately 70% over the next 20 years. Surgery, chemotherapy and radiotherapy have been used for decades as primary strategies against cancer in patients; however, cancer cell drug and radiation resistance development often leads to lower remission and higher relapse incidence. Cell therapies for cancer are emerging approaches to enhance tumor-specific killing and include expansion of patients’ tumor-infiltrating lymphocytes or complex engineering of the T cell receptor or Chimeric Antigen Receptors (CAR). The latter have shown unprecedented progress towards treating incurable cancers and are currently being examined in over 200 clinical trials. Developing successful therapeutic strategies using live cells entails the ability to determine their in vivo biodistribution and persistence after systemic administration. Non-invasive imaging techniques such as Magnetic Resonance Imaging (MRI) and Positron Emission Tomography are the best candidates for real time, quantitative assessment of tumor response. This thesis describes fluorinated imaging probes and methods for labeled cell tracking by 19F MRI. Perfluorocarbon (PFC) probes are composed of numerous fluorine atoms, which are not naturally present in the body and allow for background free quantitation of the signal. Following transfer to the subject, 19F MRI allows direct visualization of instant labeled-cell fate as well as quantification of local and systemic accumulation over time. The principle bottleneck that remains for longitudinal tracking of transferred immune cells is 19F MRI sensitivity. This work depicts strategies to increase cell loading through cell penetrating peptides. In addition, one can exploit the properties of PFC nanoemulsions to indirectly detect adoptive cell therapy cytotoxicity against cancer cells. Overall, 19F MR imaging is a versatile technique that can provide insights into the survival and modes of actions of cell therapy against cancer.