Synthesis and characterization of 18F‐labeled active site inhibited factor VII (ASIS). (27th March 2015)

• Record Type: Journal Article
• Authors: Erlandsson, Maria; Nielsen, Carsten H.; Jeppesen, Troels E.; Kristensen, Jesper B.; Petersen, Lars C.; Madsen, Jacob; Kjær, Andreas
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 58:Number 5(2015)
• Page Start: 196
• Page End: 201
• Publication Date: 2015-03-27
• Subjects: Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3282
• Languages: English
• ISSNs: 0362-4803

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <sup>18</sup>F‐labeled ASIS derivative to assess TF expression in tumors.</p> <p>Active site inhibited factor VII was labeled using <italic>N</italic>‐succinimidyl‐4‐[<sup>18</sup>F]fluorobenzoate, and the [<sup>18</sup>F]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 [<sup>18</sup>F]ASIS to TF and to a specific anti‐factor VII antibody (F1A2‐mAb). No significant difference in binding efficacy between [<sup>18</sup>F]ASIS and ASIS could be detected. Furthermore, [<sup>18</sup>F]ASIS was relatively stable <italic>in vitro</italic> and <italic>in vivo</italic> in mice.</p> <p>In conclusion, [<sup>18</sup>F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. <italic>In vivo</italic> positron emission tomography studies to evaluate the full potential of [<sup>18</sup>F]ASIS are in progress.</p> </abstract>