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

Corby Fink,Matthew S Fox,Shashank Bhatt,Jeffrey M Gaudet,Sowmya Viswanathan,Gregory A Dekaban,Paula J Foster,Michael Smith,Joseph Chin

doi:10.1038/s41598-017-19031-0

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.

Highlights

Cancer immunotherapy is an emerging research area that relies on one’s own immune system to combat the cancer
When combined with 1H Magnetic resonance imaging (MRI), the anatomical 3-dimensional location of this observed 19F signal can be determined as well[28,29,30]. This type of imaging is capable of translating in vivo 19F signal into the relative number of cells at a given location[30]. This allows the direct quantification of therapeutic cell numbers that migrate to secondary lymphoid organs or a tumor post-injection, and has the potential to serve as a non-invasive marker predictive of the immunological outcome of a cell-based cancer immunotherapy
We demonstrate that 19F-PFC-labeled peripheral blood mononuclear cells (PBMC) can be detected in a mock human in vivo system using a clinical 3 T MRI scanner and a custom-built dual 1H/19F switchable radio frequency (RF) coil suitable for use in humans

Summary

Introduction

Cancer immunotherapy is an emerging research area that relies on one’s own immune system to combat the cancer. Experiments were performed with human PBMC labeled with both 19F-PFC and CFSE prior to injection into nude mice in order to verify that the in vivo 19F signal is the result of originally injected cells. Two days following the injection of 3 × 106 human 19F-PFC PBMC into the footpad of nu/nu mice (N = 3, n = 4 per experiment), 19F MRI detected 1.31 ± 0.2 × 105 cells (Fig. 3a, yellow arrow) in the draining popliteal lymph node.

Results

Conclusion