19F-perfluorocarbon-labeled human peripheral blood mononuclear cells can be detected in vivo using clinical MRI parameters in a therapeutic cell setting

Abstract

A 19Fluorine (19F) perfluorocarbon cell labeling agent, when employed with an appropriate cellular MRI protocol, allows for in vivo cell tracking. 19F cellular MRI can be used to non-invasively assess the location and persistence of cell-based cancer vaccines and other cell-based therapies. This study was designed to determine the feasibility of labeling and tracking peripheral blood mononuclear cells (PBMC), a heterogeneous cell population. Under GMP-compliant conditions human PBMC were labeled with a 19F-based MRI cell-labeling agent in a manner safe for autologous re-injection. Greater than 99% of PBMC labeled with the 19F cell-labeling agent without affecting functionality or affecting viability. The 19F-labeled PBMC were detected in vivo in a mouse model at the injection site and in a draining lymph node. A clinical cellular MR protocol was optimized for the detection of PBMC injected both at the surface of a porcine shank and at a depth of 1.2 cm, equivalent to depth of a human lymph node, using a dual 1H/19F dual switchable surface radio frequency coil. This study demonstrates it is feasible to label and track 19F-labeled PBMC using clinical MRI protocols. Thus, 19F cellular MRI represents a non-invasive imaging technique suitable to assess the effectiveness of cell-based cancer vaccines.

A Trimodal Imaging Platform for Tracking Viable Transplanted Pancreatic Islets In Vivo: F-19 MR, Fluorescence, and Bioluminescence Imaging

“…This excess of nanoparticles could limit further agent uptake. Nevertheless, labeling using 17 mg/ml of PLGA-NPs led to the incorporation of 5.5 ± 1.8 × 10 14 of F-19 per islet (approximately 5.5 ± 1.8 × 10 11 of F-19 nuclei), a finding that accords with published data (range of 10 11 –10 13 ) [ 35 – 37 ]. The nanoparticles have been previously shown to locate intracellularly in different cell types [ 16 , 17 ].…”

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

“…Vaccines prepared from PBMCs are FDA-approved for prostate cancer treatment [ 60 ]. Fink et al [ 61 ] investigated the use of PFC agents to label human PBMC samples from patients to enable in vivo detection (Table 1 ). The authors showed that all PBMC cells label, but to varying degrees, and uptake measurements in sorted cell subtypes yielded a labeling ( 19 F/cell) profile.…”

“…The limits of detection using 19 F-based imaging ranges from ~ 10 3 to ~ 10 5 cells per voxel [ 76 ]. For a given experiment, results depend on specific details, such as the PFC molecule and nanoemulsion used, the cell type (i.e., cell cytoplasm size) labeled, viability of cell culture and commensurate label uptake, image acquisition methods, magnetic field strength, and MRI detector configuration [ 40 , 46 , 61 , 72 ]. Looking forward, there are multiple, clinically-feasible, technical avenues for improving cell detection sensitivity that are vigorously being investigated involving new probe design and data acquisition methods [ 30 , 77 , 78 ].…”

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

“…Fluorine-19 MRI methods have shown promise for the detection of cell therapy products post-transfer, 12,[14][15][16]18,19,38 inflammatory infiltrates, [39][40][41][42][43] and molecular targets 44 in vivo in preclinical models. Moreover, first-generation 19 F probes based on PFC nanoemulsions have been used in a pilot clinical trial.…”

“…12,13 Fluorine-19-based MRI nanoemulsion probes are an option for non-invasively imaging of cell populations. [14][15][16][17][18][19][20] The 19 F nuclei have high intrinsic sensitivity, with 89% relative sensitivity compared to 1 H. De minimis endogenous 19 F in the body ensures that any MRI signals collected are from the introduced tracer probe. F-dense perfluorocarbon (PFC) molecules are often used to form nanoemulsion imaging probes that can be endocytosed by cells.…”