Fluorine-19 MRI for detection and quantification of immune cell therapy for cancer

Abstract

Over the past two decades, immune cell therapy has emerged as a potent treatment for multiple cancers, first through groundbreaking leukemia therapy, and more recently, by tackling solid tumors. Developing successful therapeutic strategies using live cells could benefit from the ability to rapidly determine their in vivo biodistribution and persistence. Assaying cell biodistribution is unconventional compared to traditional small molecule drug pharmacokinetic readouts used in the pharmaceutical pipeline, yet this information is critical towards understanding putative therapeutic outcomes and modes of action. Towards this goal, efforts are underway to visualize and quantify immune cell therapy in vivo using advanced magnetic resonance imaging (MRI) techniques. Cell labeling probes based on perfluorocarbon nanoemulsions, paired with fluorine-19 MRI detection, enables background-free quantification of cell localization and survival. Here, we highlight recent preclinical and clinical uses of perfluorocarbon probes and 19F MRI for adoptive cell transfer (ACT) studies employing experimental T lymphocytes, NK, PBMC, and dendritic cell therapies. We assess the forward looking potential of this emerging imaging technology to aid discovery and preclinical phases, as well as clinical trials. The limitations and barriers towards widespread adoption of this technology, as well as alternative imaging strategies, are discussed.

Cell penetrating peptide functionalized perfluorocarbon nanoemulsions for targeted cell labeling and enhanced fluorine‐19 MRI detection

“…12 There are inherent limitations of xenograft preclinical tumor models; immunological differences, artificial tumor implants, and similar tumor size in mouse models and humans, versus vastly different doses of cytotherapy delivered to these subjects, further limit extrapolation of our model findings to human use. 24…”

“…Detailed reviews of the biomedical applications of 19 F cell detection and tracking are found elsewhere. [21][22][23][24] Engineered lymphocytes commonly used in immunotherapy 25 have an intrinsically small cytoplasmic volume and are weakly phagocytic, thereby restricting uptake of intracellular PFC label. The limits of cell detection in spin-density-weighted 19 F MRI is linearly proportional to the cell labeling levels.…”

Tracking Adoptive T Cell Therapy Using Magnetic Particle Imaging

“…Studies using other biomedical imaging modalities to track adoptively transferred T cells have also suggested that T cells accumulate in the liver, lungs, and spleen after intravenous injection. [42][43][44] Importantly, observation of both an MPI signal and DsRed fluorescence in the brain tumor suggests that viable ferucarbotran-labeled T cells were able to reach the brain glioblastoma tumor. Figure 5.…”

Advanced Cancer Imaging Applied in the Comparative Setting

“…19 F MRI is a promising approach for tracking NK cells non-invasively without toxicity or ionizing radiation. Members of our collaborative group have developed methodology to label canine NK cells with non-radioactive 19 F without compromising NK cell function and they were the first group to enumerate and track NK cells within a tumor in vivo using hot spot 19 F-MRI (69,70). We are currently evaluating the utility of a customized 19 F MR coil (Figure 10) large enough to acquire images from canines (and pediatric patients in future trials).…”