Strategies towards in vivo imaging of active transglutaminase type 2 using positron emission tomography

Berend van der Wildt; Adriaan A Lammertsma; Benjamin Drukarch; Albert D Windhorst

doi:10.1007/s00726-016-2288-y

Strategies towards in vivo imaging of active transglutaminase type 2 using positron emission tomography

Amino Acids. 2017 Mar;49(3):585-595. doi: 10.1007/s00726-016-2288-y. Epub 2016 Jul 5.

Authors

Berend van der Wildt^{1

2}, Adriaan A Lammertsma³, Benjamin Drukarch⁴, Albert D Windhorst³

Affiliations

¹ Departments of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands. b.vanderwildt@vumc.nl.
² Departments of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands. b.vanderwildt@vumc.nl.
³ Departments of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
⁴ Departments of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

Transglutaminase type 2 (TG2) is increasingly linked to the pathogenesis of several diseases, such as celiac disease, cancer, and fibrotic and neurodegenerative diseases. In parallel with becoming an attractive target for therapy, interest in the development of compounds for in vivo imaging of TG2 is rising. Such imaging biomarkers might assist in clarifying the role of TG2 in pathology and in monitoring TG2 inhibition in vivo and thus assist in drug development. In this review, the latest results together with various strategies in TG2 PET tracer development are discussed, including radiolabelling of irreversible and reversible active-site inhibitors, as well as allosteric inhibitors, acyl-donor and acyl-acceptor substrates, and anti-TG2 monoclonal antibodies.

Keywords: Antibodies; Irreversible TG2 inhibitors; PET; Reversible TG2 inhibitors; Substrates; Transglutaminase type 2.

Publication types

Review

MeSH terms

Allosteric Site
Antibodies, Monoclonal / biosynthesis
Antibodies, Monoclonal / metabolism*
Antibodies, Monoclonal / pharmacokinetics
Catalytic Domain
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / metabolism
Enzyme Inhibitors / pharmacokinetics
GTP-Binding Proteins / analysis*
GTP-Binding Proteins / genetics
GTP-Binding Proteins / metabolism
Gene Expression
Humans
Molecular Imaging / methods*
Peptides / chemical synthesis
Peptides / metabolism*
Peptides / pharmacokinetics
Positron-Emission Tomography / methods*
Protein Binding
Protein Glutamine gamma Glutamyltransferase 2
Radioisotopes / chemistry
Structure-Activity Relationship
Transglutaminases / analysis*
Transglutaminases / genetics
Transglutaminases / metabolism

Substances

Antibodies, Monoclonal
Enzyme Inhibitors
Peptides
Radioisotopes
Protein Glutamine gamma Glutamyltransferase 2
Transglutaminases
GTP-Binding Proteins