[18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species

Abstract

Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n = 1), rats (n = 4), rabbits (n = 4) and non-human primates (n = 3), via carotid artery in rats (n = 4) and non-human primates (n = 3), and via intra-myocardial injection in rats (n = 5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.

Direct Cell Radiolabeling for in Vivo Cell Tracking with PET and SPECT Imaging

“…[ 18 F]­FDG is transported across the cell membrane and into the cytoplasm via GLUT-1 transporters and is phosphorylated within the cell by hexokinase to [ 18 F]­FDG-6-phosphate (Figure A). Hence, direct cell labeling can be blocked by the presence of nonradioactive glucose . With a fluorine atom instead of a hydroxy group on the second carbon, [ 18 F]­FDG-6-phosphate cannot be isomerized and metabolized further and is trapped intracellularly.…”

“…With a fluorine atom instead of a hydroxy group on the second carbon, [ 18 F]­FDG-6-phosphate cannot be isomerized and metabolized further and is trapped intracellularly. However, the retention of 18 F inside most leukocytes and stem cells is poor, as [ 18 F]­FDG-6-P undergoes dephosphorylation back to [ 18 F]­FDG, leading to the release of 20–40% of the original activity within an hour. ,,,,, This does not preclude the use of direct cell tracking with [ 18 F]­FDG for in vivo imaging applications within a short time framethere have been several clinical studies using [ 18 F]­FDG-labeled cells (section ), but this radiotracer has yet to see routine use as a cell labeling agent. Furthermore, released [ 18 F]­FDG is then taken up by neighboring tissue cells, leading to an artificial increase in signal which is not a true reflection of the presence of the administered cells (Figure ).…”

Mesenchymal Stem Cell Therapy: Hope for Patients With Systemic Lupus Erythematosus

“…We summarize the potential causes of MSC therapy inefficacy in SLE from the following aspects: the defective BM-MSCs in patients with SLE, the expansion of MSCs in vitro, and the complex microenvironment in patients with SLE. It is worth noting that studies in many other diseases have confirmed that most intravenously infused MSCs could be trapped and cleared in the lung (72)(73)(74), which may be one of the reasons for MSC therapy inefficacy.…”

“…The pretreatment of MSCs with miR-9-5p or TNF-a could also improve the migration ability of MSCs, whereas the inhibition of miR-9-5p reduced MSC migration (123,124). For the systemic immune responses of MSCs, many studies observed the phenomenon that most of the MSCs were trapped in the lung after IV infusion in murine models (72)(73)(74). For the mechanisms, the MSCs trapped in the lung after IV infusion may secret bioactive molecules and EVs into the blood and efficiently regulate systemic immune responses (125,126).…”

Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice

“…There are various non-invasive molecular imaging modalities that could be employed to track cell based therapies including optical imaging via fluorescence imaging (FLI) 1 , 2 , bioluminescence imaging (BLI) 3 , 4 , and ultrasound-guided photoacoustic imaging (PA) 5 – 7 . Radiology imaging including magnetic resonance imaging (MRI) 8 – 10 , computed tomography (CT) 11 – 13 , and nuclear medicine imaging such as positron emission tomography (PET) 14 – 18 and single photon emission computed tomography (SPECT) 19 , 20 , could also be employed to effectively measure the distribution, localization, and clearance of various cell-based therapies over time and to shed light on safety and efficacy.…”