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

Abstract

PurposeCellular 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.MethodsThe 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.ResultsSpin-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.ConclusionThese 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.

19F-MRI for monitoring human NK cellsin vivo

“…DCs were detected 4 h post inoculation with a 50% decrease in 19 F signal at the site of injection by 24 h post inoculation in two patients. 34 These data demonstrate the feasibility to visualize human immune cells using Several other imaging techniques have been used in pre-clinical or clinical scenarios to monitor NK cells in recipients and monitor the tumor response. These techniques include positron emission tomography (PET), single photon emission computed tomography (SPECT), and optical imaging (OI) (bioluminescence and fluorescence imaging).…”

“…To date, investigators have successfully used this approach to track murine macrophages, 24 19 F-MRI without apparent toxicity. 34 However, NK cells have been challenging to label using this approach 35 and data is lacking on NK cell trafficking even though they are being infused in clinical trials.…”

“…25,26 Other investigators have also reported on the ability to ex vivo label other potential cell therapies with 19 F, including murine 30 and human neural stem cells, 31 human CD34 C hematopoietic stem cells (HSCs) and mouse bone marrow derived HSCs as well as murine 32 and human 33 19 F-MRI without apparent toxicity. 34 About 10 million DCs were injected intradermally into quadriceps and patients were imaged for about 9.5 min. DCs were detected 4 h post inoculation with a 50% decrease in 19 F signal at the site of injection by 24 h post inoculation in two patients.…”

“…The strength of our MRI is closer to the field strength of MRIs in clinical practice today, making our imaging methodology more relevant for clinical imaging of ACT. 34 One obvious limitation of our MRI coil was in the inability to detect 19 F-labeled NK cells after intravenous (i.v.) infusion (data not shown), the most common route of therapy.…”

Gold nanoparticles protected by fluorinated ligands: Syntheses, properties and applications

“…In this respect, it is important to stress that some fluorinated compounds such as the perfluoro alkanoic and perfluorosulfonic acids, indeed display non-negligible long term toxicity. Interesting building blocks in the design of the nanoparticles' monolayer are perfluoropolyethers, these compounds are being extensively studied as 19 F MRI tracers in vitro and in vivo [49][50][51] and the data support a limited toxicity. Given the low cytotoxicity of these systems, application for cell tracking in vivo could be foreseen in analogy to nanoemulsion containing perfluoropolyether (PFPE) described by Ahrens [52,53].…”