title: Strategies towards in vivo imaging of active transglutaminase type 2 using positron emission tomography.
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.
authors.affiliation: Departments of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands. b.vanderwildt@vumc.nl.|Departments of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands. b.vanderwildt@vumc.nl.
authors.forename: Berend
authors.identifier: 0000-0001-5503-2382
authors.initials: B
authors.lastname: van der Wildt
authors.affiliation: Departments of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: Departments of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drukarch
authors.affiliation: Departments of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
mesh_terms: D000495:Allosteric Site; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics; D019204:GTP-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D057054:Molecular Imaging / Q000379:methods*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011868:Radioisotopes / Q000737:chemistry; D013329:Structure-Activity Relationship; D011503:Transglutaminases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D010455:Peptides; D011868:Radioisotopes; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Antibodies; Irreversible TG2 inhibitors; PET; Reversible TG2 inhibitors; Substrates; Transglutaminase type 2