Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine‐19 MRI

Abstract

Purpose Cellular therapeutics are emerging as a treatment option for a host of serious human diseases. To accelerate clinical translation, noninvasive imaging of cell grafts in clinical trials can potentially be used to assess the initial delivery and behavior of cells. Methods The use of a perfluorocarbon (PFC) tracer agent for clinical fluorine‐19 (19F) MRI cell detection is described. This technology was used to detect immunotherapeutic dendritic cells (DCs) delivered to colorectal adenocarcinoma patients. Autologous DC vaccines were labeled with a PFC MRI agent ex vivo. Patients received DCs intradermally, and 19F spin‐density‐weighted MRI at 3 Tesla (T) was used to observe cells. Results Spin‐density‐weighted 19F images at the injection site displayed DCs as background‐free “hot‐spot” images. 19F images were acquired in clinically relevant scan times (<10 min). Apparent DC numbers could be quantified in two patients from the 19F hot‐spots and were observed to decrease by ∼50% at injection site by 24 h. From 3T phantom studies, the sensitivity limit for DC detection is estimated to be on the order of ∼105 cells/voxel in this study. Conclusion These results help to establish a clinically applicable means to track a broad range of cell types used in cell therapy. Magn Reson Med 72:1696–1701, 2014. © 2014 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance.

Development and Characterization of Resveratrol Nanoemulsions Carrying Dual-Imaging Agents

“…Delivering resveratrol with PFPE nanoemulsions hence provides a unique advantage over other formulations, as 19 F MRI is already demonstrated as a safe, quantitative imaging technique in humans [32]. Hence, the presence of PFPE will allow for the evaluation of resveratrol nanoemulsion biodistribution in human studies in the future.…”

ERK1 as a Therapeutic Target for Dendritic Cell Vaccination against High-Grade Gliomas

“…Notwithstanding the role of Cdc42 in DC polarity and orientation during antigen presentation to T cells (32) (46), it might offer significant advantages in the future over other methods to track DC migration such as scintigraphy combined with radioisotope 111 In-oxine (47). MRI in general was shown to be better at localizing DC vaccines in vivo (48); paramagnetic iron oxide nanoparticles were used to label and follow cells in melanoma patients (48).…”

“…The main hurdle is signal sensitivity, which can pose a challenge when imaging 19 F-labeled DCs in cancer patients (46). In a recent report, we aimed to promote the signal achieved per unit cell; we enriched 19 F nanoparticles with the phosphatidylethanolamine DPPE and observed a stronger enhancement of 19 F signal (from 74 to 771 nmol) per 10 6 cells, which equates to an order of magnitude increase in 19 F spins from 0.89 Â 10 12 19 F spins (control nanoparticles) to 0.93 Â 10 13 19 F spins (in DPPEenriched nanoparticles) per DC unit (19).…”

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

“…19 F) labeling might be a promising alternative for cell imaging, because it has little effect on stem cell viability, proliferation, and differentiation [23][24][25]. Furthermore, 19 F MRI has no significant background signal from host tissue [26] and has been used in a cell therapy-based clinical trial [27]. However, many MRI facilities lack the specialized equipment required for 19 F MR image acquisition, thereby reducing the accessibility of this technique [28].…”