N1'-(p-[18F]Fluorobenzyl)naltrindole (p-[18F]BNTI) as a potential PET imaging agent for DOP receptors

Abstract

SummaryThe N1'-(p-fluorobenzyl)naltrindole 5 has been synthesized by reaction of 3-O-benzyl NTI 3 with p-fluorobenzylbromide under phase transfer catalysis. The subsequent 3-O-benzyldeprotection of 4 in HBr/CH 3 COOH gave the target compound 5 in three steps from naltrindole 2. p-FBNTI 5 is a novel delta opioid receptor antagonist (K i =0.00312 nM) and antagonizes the delta opioid (DOP) agonist, DPDPE, with a K e =1.55 nM in the mouse vas deferens preparation. Using the same synthetic strategy the synthesis of p-[18 F]BNTI 10 was undertaken. The final yield was 4% and the specific activity varied in a range of 250-400 mCi/mmol.

Syntheses of meta‐[18F]fluorobenzaldehyde and meta‐[18F]fluorobenzylbromide from phenyl(3‐Formylphenyl) iodonium salt precursors

“…18 F‐labeled fluorobenzaldehydes and fluorobenzylbromides represent useful synthons for the preparation of PET radiopharmaceuticals 21–24. Although ortho‐ and para‐ [ 18 F]fluorobenzaldehydes can easily be prepared with high yields by nucleophilic substitution reactions where corresponding nitro groups or quaternary amines are replaced by [ 18 F]F − , the corresponding meta‐ derivatives are more problematic.…”

FBNTI, a DOR-Selective Antagonist That Allosterically Activates MOR within a MOR–DOR Heteromer

“…25 The mouse MVD assay revealed that FBNTI functions as a potent antagonist of DPDPE (K e = 1.59 nM). 10 The in vivo FBNTI antinociception is therefore most likely initiated by its interaction with the DOR protomer of a MOR−DOR heteromer that leads to allosteric activation of the MOR protomer (Figure 3). DOR Knockout Studies.…”

Positron emission tomography radioligands for the opioid system

“…In research that has only appeared in extended abstract form, Sajjad et al described the radiochemical synthesis of [ 11 C]naltriben (Figure 8), a d 2 subtype specific radioligand, from [ 11 C]cyclopropylcarbonyl chloride and its biodistribution in mice. 54 Other than initial comments in the abstract of comparable results in comparison to [ 11 55 No further studies have been reported with this tracer. It appears that [ 11 C]MeNTI is still the radioligand of choice for PET studies targeting d-opioid receptors.…”

“…The Portoghese group continues to develop new ligands for opiate receptor subtypes. The most recent PET δ‐opiate radioligand from these investigators is the p ‐[ 18 F]fluorobenzyl analog of MeNTI prepared at moderate specific activity in a multistep radiochemical synthesis from [ 18 F]fluoride via p ‐[ 18 F]fluorobenzyl bromide . No further studies have been reported with this tracer.…”