First no‐carrier‐added radioselenation of an adenosine‐A₁ receptor ligand

Abstract

SummaryThe precursor synthesis and the no-carrier-added (n.c.a.) radiosynthesis of the adenosine-A 1 receptor ligand 5Se]1) are described in this report. A method was developed starting from elemental n.c.a. selenium-75, followed by a three-step polymer-supported radioselenation and deprotection which gave the radioligand with a radiochemical yield of 30%, a radiochemical purity of >99% and a specific radioactivity of >300 GBq/mmol (8 Ci/ mmol). Preparation time was 40 min. The nonradioactive compound 5 0 -(methylseleno)-N 6 -cyclopentyladenosine (1) was pharmacologically evaluated in vitro and showed high affinity and selectivity for the adenosine-A 1 receptor. These preliminary results suggest that this compound could be a useful radioligand for the noninvasive imaging of the brain adenosine-A 1 receptors using positron emission tomography (PET) when labelled with the positron emitter selenium-73 (half-life: 7.1 h).

Labelling with positron emitters of pnicogens and chalcogens

“…If 73 Se is used as a radiolabel, the achievable specific activity would be higher in case of a large-scale synthesis, and it is expected that the obtainable specific activity would be sufficient to perform in vivo receptor studies with 73 Se-labelled ligands using PET. 167 Ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, is one of the few examples of organoselenium-containing pharmaceuticals. Ebselen shows a glutathione peroxidase-like, thiol-dependent, hydroperoxide-reducing activity and neuroprotective and cytoprotective properties and inhibits radically induced apoptosis while exhibiting low toxicity.…”

“…The high‐affinity partial agonist for the adenosine A 1 receptor, 5′‐(methyl[ 75 Se]seleno)‐ N 6 ‐cyclopentyladenosine (cf Scheme ), was obtained by the free and polymer‐supported selenourea methods (cf Scheme , pathway D) with an RCY of about 30%, within a total reaction time of 135 and 40 minutes, respectively. The method using [ 75 Se]selenocyanate as a labelling intermediate (cf Scheme , pathway C) failed in this case. The specific activity of nca 5′‐(methyl[ 75 Se]seleno)‐ N 6 ‐cyclopentyladenosine was determined to be more than 300 GBq/mmol, which is a relatively low value, but it was measured with low activity amounts of 75 Se.…”

“…The specific activity of nca 5′‐(methyl[ 75 Se]seleno)‐ N 6 ‐cyclopentyladenosine was determined to be more than 300 GBq/mmol, which is a relatively low value, but it was measured with low activity amounts of 75 Se. If 73 Se is used as a radiolabel, the achievable specific activity would be higher in case of a large‐scale synthesis, and it is expected that the obtainable specific activity would be sufficient to perform in vivo receptor studies with 73 Se‐labelled ligands using PET …”

The Adenosinergic System

“…Xanthine derivatives, such as [ 11 C]KF15372, [ 11 C]MPDX, [ 11 C]EPDX and [ 18 F]CPFPX, were synthesized as candidates for in vivo imaging of A 1 in brain (Bauer et al 2003a,b;Fukumitsu et al 2003;Ishiwata et al1995Ishiwata et al , 2007. Another radiotracer labelled with the positron emitter 75 Se has been developed for A 1 imaging (5'-(methyl[ 75 Se]seleno)-N 6 -cyclopentyladenosine), but no biological evaluation of this radiotracer has been reported (Blum et al 2004). Another radiotracer labelled with the positron emitter 75 Se has been developed for A 1 imaging (5'-(methyl[ 75 Se]seleno)-N 6 -cyclopentyladenosine), but no biological evaluation of this radiotracer has been reported (Blum et al 2004).…”

PET Tracers for Mapping Adenosine Receptors as Probes for Diagnosis of CNS Disorders

“…The other radioligand labeled with positron emitter was 5'-(methyl[ 75 Se]seleno)-N 6 -cyclopentyladenosine ( 75 Se, half life of 7.1 h) [68], but the biological evaluation of the tracer has not been reported. Table 1); however, the latter was much more stable metabolically in humans than the former [71,73].…”