A1 Refereed original research article in a scientific journal
Exploring the radiosynthesis and in vitro characteristics of [Ga-68]Ga-DOTA-Siglec-9
Authors: Jensen Svend B, Käkelä Meeri, Jodal Lars, Moisio Olli, Alstrup Aage KO, Jalkanen Sirpa, Roivainen Anne
Publisher: WILEY
Publication year: 2017
Journal: Journal of Labelled Compounds and Radiopharmaceuticals
Journal name in source: JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
Journal acronym: J LABELLED COMPD RAD
Volume: 60
Issue: 9
First page : 439
Last page: 449
Number of pages: 11
ISSN: 0362-4803
eISSN: 1099-1344
DOI: https://doi.org/10.1002/jlcr.3525
Abstract
Vascular adhesion protein 1 is a leukocyte homing-associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283-297 of sialic acid-binding IgG-like lectin 9 (Siglec-9) "CARLSLSWRGLTLCPSK" bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([Ga-68]Ga-DOTA-Siglec-9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [Ga-68]GaDOTA- Siglec-9 are presented and compared with previously published methods. A simple, robust radiosynthesis of [Ga-68]Ga-DOTA-Siglec-9 with a yield of 62% (non decay-corrected) was identified, and it had a radiochemical purity > 98% and a specific radioactivity of 35 MBq/nmol. Furthermore, the protein binding and stability of [Ga-68]Ga-DOTA-Siglec-9 were analyzed in vitro in mouse, rat, rabbit, pig, and human plasma and compared with in vivo pig results. The plasma in vitro protein binding of [Ga-68]Ga-DOTA-Siglec-9 was the lowest in the pig followed by rabbit, human, rat, and mouse. It was considerably higher in the in vivo pig experiments. The in vivo stability in pigs was lower than the in vitro stability. Despite considerable species differences, the observed characteristics of [Ga-68]Ga-DOTA- Siglec-9 are suitable as a positron emission tomography tracer.
Vascular adhesion protein 1 is a leukocyte homing-associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283-297 of sialic acid-binding IgG-like lectin 9 (Siglec-9) "CARLSLSWRGLTLCPSK" bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([Ga-68]Ga-DOTA-Siglec-9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [Ga-68]GaDOTA- Siglec-9 are presented and compared with previously published methods. A simple, robust radiosynthesis of [Ga-68]Ga-DOTA-Siglec-9 with a yield of 62% (non decay-corrected) was identified, and it had a radiochemical purity > 98% and a specific radioactivity of 35 MBq/nmol. Furthermore, the protein binding and stability of [Ga-68]Ga-DOTA-Siglec-9 were analyzed in vitro in mouse, rat, rabbit, pig, and human plasma and compared with in vivo pig results. The plasma in vitro protein binding of [Ga-68]Ga-DOTA-Siglec-9 was the lowest in the pig followed by rabbit, human, rat, and mouse. It was considerably higher in the in vivo pig experiments. The in vivo stability in pigs was lower than the in vitro stability. Despite considerable species differences, the observed characteristics of [Ga-68]Ga-DOTA- Siglec-9 are suitable as a positron emission tomography tracer.
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