Preparation of a bromine-76 labelled analogue of epibatidine: a potent ligand for nicotinic acetylcholine receptor studies

Kassiou, Michael; Loc’h, Christian; Dollé, Frédéric; Musachio, John L.; Dolci, Lilian; Crouzel, C.; Dannals, Robert F.; Mazièré, B.

doi:10.1016/s0969-8043(02)00187-2

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…It is interesting to note that there are very few papers in the recent literature on the use of 75 Br and 77 Br, but several on the use of 76 Br. 22,23 This is probably due to the fact that 76 Br is a positron emitter with a longer half-life (16 h) than 75 Br, and has a higher abundance of positron emission than 77 Br.…”

Section: Bromine-75 -76 -77mentioning

confidence: 99%

Radiohalogens for imaging and therapy

2005

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Radiohalogens play a very important role in radiopharmaceuticals used for medical imaging (now referred to as molecular imaging) and therapy applications. Development of new radiopharmaceuticals that have radiohalogens incorporated requires an understanding of parameters that are unique to chemistry involving these radionuclides. Those parameters include requirement for production and purification of the halogen radionuclides, as well as development of reaction conditions for use with high specific activity short-lived radionuclides. In this tutorial review, several radiohalogens, their radiolabeling chemistry and their application to medical imaging and therapy are discussed.

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Section: Bromine-75 -76 -77mentioning

confidence: 99%

Radiohalogens for imaging and therapy

2005

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“…The only significant contribution to the total activity 16 hours post EOB is due to 76 Br. There is < 1% 75 Br and 77 Br Numerous preparations of lower specific activity radiobrominated pharmaceuticals are reported in the literature [16][17][18][19][20]. The low SA is due to carrier bromide present in the target material, reagents, or solvents.…”

Section: Resultsmentioning

confidence: 99%

Semi-remote production of Br-76 and preparation of high specific activity radiobrominated pharmaceuticals for PET studies

Szajek¹,

Kao²,

Kiesewetter³

et al. 2004

Radiochimica Acta

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The PET radionuclide 76 Br (t 1/2 = 16.2 h) can be easily produced utilizing the nuclear reaction As( 3 He, 2n) 76 Br. We use high-purity arsenic targets and isolate radioactive bromide by chromic acid oxidation followed by simple distillation of [ 76 Br] hydrogen bromide using a semi-remote apparatus. Use of reagents with little or no carrier bromine yields high specific activity radiobrominated pharmaceuticals prepared from the distilled [ 76 Br] hydrogen bromide.

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“…The synthesis of [ 76 Br]BrPH has been previously described (Kassiou et al, 2002). Briefly, the iodinated analog (norchloroiodoepibatidine, IPH) in ethanol was added to NH 4 76 Br, CuSO 4 ⅐5H 2 O, and Na 2 S 2 O 5 in an acetic acid solution.…”

Section: Materials and Methods Radioligandmentioning

confidence: 99%

“…However, PET studies in nonhuman primates with [ 18 F]NFEP and SPECT studies with [ 123 I]IPH have confirmed the potential of the halogenated derivatives of epibatidine for mapping nAChRs (Ding et al, 1996;Musachio et al, 1997) and they continue to demonstrate utility in receptor occupancy and mechanistic studies in animals (Ding et al, 2000a,b;. We recently reported on the preparation of a bromine analog of epibatidine labeled with bromine-76, a longer half-life positron emitter, (T1/2 ϭ 16.2 h) ([ 76 Br]BrPH) (Kassiou et al, 2002). The longer half-life of bromine-76 allows in vitro binding and autoradiography experiments to be performed easily and PET imaging which would not require decay correction when compared to fluorine-18.…”

Section: Introductionmentioning

confidence: 95%

Pharmacological evaluation of a Br‐76 analog of epibatidine: A potent ligand for studying brain nicotinic acetylcholine receptors

Kassiou

Bottlaender

Loc’h

et al. 2002

Synapse

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[(76)Br]-Norchlorobromoepibatidine ([(76)Br]BrPH) is a specific and high affinity radioligand for the nicotinic acetylcholine receptors (nAChRs). In vitro, on rat thalamus membranes [(76)Br]BrPH bound to two sites with apparent affinities of 8 pM and 3 nM. The density of binding sites were 1.9 and 70 fmol/mg protein, respectively. In vivo, in biodistribution and autoradiographic studies in rats the regional distribution of [(76)Br]BrPH paralleled the neuroanatomical localization of nAChRs. Two hours postinjection, the highest concentration in the brain was found in thalamus and colliculi (4% ID/g). Competition experiments with specific nicotinic, muscarinic, dopaminergic, and serotoninergic drugs confirmed that the in vivo binding of [(76)Br]BrPH was consistent with neuronal nicotinic receptors. PET imaging of [(76)Br]BrPH in baboon demonstrated a rapid and high uptake in the brain. Peak uptake occurred at 30-40 min for the thalamus. Due to the constant washout in the cerebellum, the thalamus to cerebellum ratio was 5 at 2 h postinjection. Subcutaneous injection of cytisine (1 mg/kg), 3 h postinjection of [(76)Br]BrPH reduced the radioactivity concentration in thalamus and cortex by 58 and 50%, respectively, as observed 1 h later. Cytisine pretreatment (5 mg/kg s.c.) inhibited completely the radioligand accumulation in the thalamus. Chronic MPTP pretreatment resulted in reduction of [(76)Br]BrPH uptake in all brain regions except in cerebellum. These preliminary results suggest that [(76)Br]BrPH has the potential to be a useful radioligand for studying the pharmacology of nicotinic acetylcholine receptors in preclinical experiments.

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Preparation of a bromine-76 labelled analogue of epibatidine: a potent ligand for nicotinic acetylcholine receptor studies

Cited by 11 publications

References 29 publications

Radiohalogens for imaging and therapy

Radiohalogens for imaging and therapy

Semi-remote production of Br-76 and preparation of high specific activity radiobrominated pharmaceuticals for PET studies

Pharmacological evaluation of a Br‐76 analog of epibatidine: A potent ligand for studying brain nicotinic acetylcholine receptors

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