¹⁸F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis

Abstract

Center at UCLA. ONW and CGR are inventors on a patent held by the University of California Regents that discloses 18 F-FAC. There are no other potential conflicts of interest.

Longitudinal Imaging of T Cells and Inflammatory Demyelination in a Preclinical Model of Multiple Sclerosis Using 18F-FAraG PET and MRI

“…Recent work by Chen et al. described 1-(2′-deoxy-2′- 18 F-fluoroarabinofuranosyl) cytosine ( 18 F-FAC) use in the EAE model ( 22 ). 18 F-FAC has been shown to accumulate in leukocytes through cytoplasmic deoxycytidine kinase phosphorylation in models of immune activation ( 23 , 24 ) and accumulated in nearly equal amounts within brain-infiltrating T cells and innate immune cells.…”

Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy

“…[ 18 F]FAC is more selective for lymphoid organs than [ 18 F]FDG and [ 18 F]FLT; however, the baseline retention in lymphoid organs is higher and could hinder the detection of weak immune responses [93]. Additionally, Chen et al demonstrated that activated leukocytes labelled with [ 18 F]FAC can cross the blood-brain-barrier and be used to visualize leukocyte accumulation in the brain using an experimental autoimmune encephalomyelitis model [130]. A drawback of this tracer is the long synthesis time and rapid in vivo deamination of [ 18 F]FAC, making it less suitable for regular use in the clinic [131].…”

Opportunities for Molecular Imaging in Multiple Sclerosis Management: Linking Probe to Treatment

“…At the present time, imaging probes are available clinically to monitor most CNS cell types; however, they have yet to be explored for MS applications. Differences among animal species (eg, BBB permeability) remain an obstacle for developing and translating targeted molecular imaging probes for MS applications, as exemplified by the limited PET signal of 2-chloro-2'-deoxy-2'-fluoro-9-b-darabinofuranosyl-adenine (33) in the human brain.…”

“…Uptake of the latter two probes was only observed in some lesions ex vivo (autoradiography). Their limited uptake may be a reflection of more inflamed regions during the acute stages of lesion development or may be due to an inability to cross the BBB as observed with 2-chloro-2'-deoxy-2'-fluoro-9-b-d-arabinofuranosyl-adenine, another nucleoside probe (33). In another study (53), FDG uptake was related to PK-11195, a probe for translocator protein, and S-4-(3-fluoropropyl)-l-glutamic acid (FSPG), a probe for glutamate and/or cysteine antiporter activity; however, only FSPG could monitor disease activity in a rat MS model.…”