Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS). / Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer; Kristensen, Jesper B.; Petersen, Lars C.; Madsen, Jacob; Kjaer, Andreas.
In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 58, No. 5, 05.2015, p. 196-201.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)
AU - Erlandsson, Maria
AU - Nielsen, Carsten Haagen
AU - Jeppesen, Troels Elmer
AU - Kristensen, Jesper B.
AU - Petersen, Lars C.
AU - Madsen, Jacob
AU - Kjaer, Andreas
N1 - Copyright © 2015 John Wiley & Sons, Ltd.
PY - 2015/5
Y1 - 2015/5
N2 - Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an 18F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[18F]fluorobenzoate, and the [18F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [18F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [18F]ASIS and ASIS could be detected. Furthermore, [18F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [18F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [18F]ASIS are in progress.
AB - Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an 18F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[18F]fluorobenzoate, and the [18F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [18F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [18F]ASIS and ASIS could be detected. Furthermore, [18F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [18F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [18F]ASIS are in progress.
U2 - 10.1002/jlcr.3282
DO - 10.1002/jlcr.3282
M3 - Journal article
C2 - 25820758
VL - 58
SP - 196
EP - 201
JO - Journal of Labelled Compounds and Radiopharmaceuticals
JF - Journal of Labelled Compounds and Radiopharmaceuticals
SN - 0362-4803
IS - 5
ER -
ID: 134952913