Immunotherapy is emerging as an exciting new approach to cancer therapy that often has fewer side effects compared to traditional combinations of radiation, chemotherapy, and surgery. MD Anderson is a leader in NK cell therapy development with more than a dozen active clinical trials including the first in human, FDA-approved, Phase-I clinical trial (NCT02271711) for children with recurrent brain tumors. Unfortunately, little is known about the biodistribution of NK cells after administration. Imaging strategies that allow visualization of their distribution could provide invaluable new information to help guide the development of optimized cancer therapies. 19F perfluorocarbon (PFC)-b...

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Immunotherapy is emerging as an exciting new approach to cancer therapy that often has fewer side effects compared to traditional combinations of radiation, chemotherapy, and surgery. MD Anderson is a leader in NK cell therapy development with more than a dozen active clinical trials including the first in human, FDA-approved, Phase-I clinical trial (NCT02271711) for children with recurrent brain tumors. Unfortunately, little is known about the biodistribution of NK cells after administration. Imaging strategies that allow visualization of their distribution could provide invaluable new information to help guide the development of optimized cancer therapies. 19F perfluorocarbon (PFC)-based contrast agents create a positive signal in 19F magnetic resonance imaging (MRI) that is easily co-registered with traditional anatomic MRI. Recently, our team has demonstrated the feasibility of NK cell labeling with a commercially available PFC label, and we have identified several opportunities for improving 19F MRI sensitivity prior to clinical translation. We will pursue multiple parallel pathways to enhance the sensitivity of 19F MRI of labeled NK cells by more than an order of magnitude, to reduce the threshold of detectability (in labeled cells per voxel), improve image resolution, and/or reduce scan time to improve patient comfort. In the first Aim of this project, we will develop new 19F PFC labels that improve sensitivity. In the second Aim, we will optimize cell labeling protocols and determine the sensitivity limits on preclinical (7T) and clinical (3T) MRI scanners. In the final Aim of this project, we will use our optimized 19F probes to characterize NK cell immunotherapy in a murine model of brain cancer. At completion of this project, we will have developed a combination of optimized new agents and methods for NK cell imaging with high sensitivity that are primed for clinical translation.

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