Radioligand synthesis

Mathews WB, Ravert HR, Musachio JL, Frank RA, Rinaldi-Carmona M, Barth F, Dannals RF. Synthesis of [1SF] SR144385 a selective radioligand for positron emission tomographic studies of brain cannabinoid receptors. J Labelled Compd Radiopharm 1994 42 589-596. 

Keywords. [ F] Fluorine, [ F] Fluoride, Positron emitter. Synthesis, Radioligand... 

M.R. Akula, C.D.P. Longford, G.W. Kabalka, Synthesis of 2-[ F]fluorobenzidine A precursor to bisdiazodyes Potential radioligands to image amyloid deposits in the brain of alzheimer patients, J. Label. Compds Radiopharm. 42 (1999) S541-S542. 

C.Y. Shiue, L.Q. Bai, R. Teng, A.P. Wolf, Application of the nucleophilic substitution reactions to the synthesis of NCA F-labeled radioligands, J. Label. Compds Radiopharm. 23 (1986) 1038-1039. 

F. Dolle, H. Valette, M. Bottlaender, F. Hinnen, F. Vaufrey, I. Guenther, C. Crouzel, Synthesis of 2-[ F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine, a highly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors, J. Label. Compds Radiopharm. 41 (1998) 451 63. 

Radioligand, [reference] R Radiochemical yield (%) Synthesis time (min) Specific activity (GBq/pmol)... 

Table 3. Synthesis of p F]fluoroisopropyl-substituted radioligands with a 1-[ F]fluoroisopropyl building block... 

Recently, the 2-[ F]fluoroethylation of a phenolic desalkyl precursor based on the jSi-AR-selective antagonist ICI 89,406 was realized via a two-step synthesis starting with the [ F]fluorination of ethylene glycol di-p-tosylate. The radiosynthesis yielded (S)-A/-[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-A/ -[4-(2-[ F]fluoroethoxy)-phenyl]-urea 10, representing a potent F-labeled high affinity / i-AR-selective radioligand with a / i-AR-selectivity of >40.000 (Fig. 15) [107],... 

LABELLING METHODS USED IN THE SYNTHESIS OF RADIOLIGANDS FOR THE HISTAMINE H3 RECEPTOR... 

H]GR 168320 was developed as a (stably labelled) tritiated H3 antagonist and evaluated for its in vitro use as a radioligand for the H3 receptor [29], As has been shown for thioperamide, the tritium labels at the 2 and 5 position of the imidazole moiety and at the 4 position of the piperidine moiety are sensitive to exchange with hydrogen from the storage solution. [3H]GR 168320 is labelled at the cyclohexane, by a catalytic reduction with 3H2, no details about the synthesis have been published (scheme 11). [3H]GR 168320 was isolated with a specific activity of 4.8 Ci/mmol. 

Choice of Radioligand. A 11+C radiolabel will probably exist for most pesticides which will be considered for radioimmunoassay development. Such an intrinsic radiolabel will prove very valuable in titering antisera and possibly in numerous other steps from antigen synthesis through assay development. Unfortunately, for the actual assay, the commonly available 11+C radiolabels may not be of high enough specific activity. The theoretical limit on the specific activity of a single carbon atom is 63 mCi/mmole, and few pesticides have a specific activity of over 50 mCi/mmole even when they are labeled in... 

This may require custom synthesis as there are only a limited number of radioligands commercially available (from NEN or Amersham-Pharmacia)... 

H]-prazosin, 128, which is an ai-adreno-radioligand, has been prepared117 in a four-step synthesis starting from furoic acid and involving reductive catalysed denomination with tritium gas (equation 50). The specific activity and radiochemical purity of the product 128 were 22.6 Ci mmol-1 and 98%, respectively. 

Raab CE, Butcher JW, Connolly TM, Karczewski J, Yu NX, Staskiewicz SJ, et al. Synthesis of the first sulfur-35-labeled hERG radioligand. Bioorg Med Chem Lett 2006 16 1692-5. 

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