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New microwave assisted radiolabelling method and rat brain biodistribution study of two new 99mTc-tricarbonyl complexes as potential brain imaging agents

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EN
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EN
Two new cyclopentadienyl piperidine derivatives, namely ferrocene carboxylic acid 1-ethyl-3-hydroxypiperidinyl ester and ferrocene carboxylic acid 4-hydroxypiperidinyl ester, were synthesized. The ligands were then radiolabelled with 99mTc using two different approaches. The first method consisted of reacting the ligand precursor with Mn(CO)5Br in pertechnetate 99mTcO4 - in normal saline and dimethyl formamide (DMF) at 150°C for 1 h. The yields were 70% and 90%, respectively. For the second method, the reactions mixtures were placed in a microwave oven for 2 min at 650 watt. The yields were higher than 90% for both 99mTc complexes. Biodistribution studies showed that tricarbonyl{eta5- [carboxy-3-hydroxy(N-ethyl)piperidine]cyclopentadienyl}technetium(I) had the highest brain uptake. The regional distribution in the brain also demonstrated relatively higher uptake of tricarbonyl{eta5-[carboxy-3-hydroxy(N-ethyl) piperidine]cyclopentadienyl}technetium(I) in the colliculus (1.97% ID/g tissue,) with the colliculus to cerebellum ratio of 1.99. We conclude that the radiolabelling can be achieved by microwave activation, and tricarbonyl{eta5-[carboxy-3- hydroxy(N-ethyl)piperidine]cyclopentadienyl}technetium(I) has the potential for use as central nervous system (CNS) imaging agent.
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97--101
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Bibliogr. 18 poz., rys.
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autor
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  • Radiopharmacy Department, Royal Liverpool University Hospital, Prescot Str., Liverpool, L7 8XP England, UK, Tel.: +44 798 888 0656, Fax: +44 151 706 4522, moez.trabelsi@gmail.com
Bibliografia
  • 1. Heimbold I, Drews A, Syhre R, Kretzschmar M, Pietzsch HJ, Johannsen B (2002) A novel technetium-99m radioligand for the 5-HT1A receptor derived from desmethyl-WAY-100635 (DWAY). Eur J Nucl Med 29:82–87
  • 2. Hoepping A, Reisgys M, Brust P et al. (1998) TROTEC-1:A new high-affinity ligand for labeling of the dopamine transporter. J Med Chem 41:4429–4432
  • 3. Johannsen B, Pietzsch HJ (2002) Development of technetium-99m-based CNS receptor ligands: have there been any advances? Eur J Nucl Med 29:263–275
  • 4. Kretzschmar M, Saidi M, Bergmann R (2003) 99mTccytectrene complexes – chemical structure and biobehaviour.Part 1: Chemical characterisation of Tc and Re complexes. In: Annual Report 2002, Institute of Bioinorg and Radiopharm Chem FZR-363:53
  • 5. Kung HF, Kim HJ, Kung MP, Meegalla SK, Plossl K,Lee HK (1996) Imaging of dopamine transporters in humans with technetium-99m TRODAT 1. Eur J Nucl Med 23:1527–1530
  • 6. Mahmood A, Kronauge JF, Barbarics E et al. (eds) (1999)Technetium, rhenium and other metals in chemistry and nuclear medicine. Vol. 5. SGE Editoriali Padova
  • 7. Mannhold R, Dross K (1996) Calculation procedures for molecular lipophilicity: a comparative study. Quant Struct Act Relat 15:403–409
  • 8. Meegalla SK, Plossl K, Kung MP et al. (1995) First example of a 99mTc complex as a dopamine transporter imaging agent. J Am Chem Soc 117:11037–11038
  • 9. Meegalla SK, Plossl K, Kung MP et al. (1996) Tc-99mlabeled tropanes as dopamine transporter imaging agents. Bioconj Chem 7:421–429
  • 10. Meegalla SK, Plossl K, Kung MP et al. (1997) Synthesis and characterization of technetium-99m-labeled tropanes as dopamine transporter-imaging agents. J Nucl Med 40:9–17
  • 11. Meegalla SK, Plossl K, Kung MP et al. (1998) Specificity of diastereomers of [99mTc]TRODAT-1 as dopamine transporter imaging agents. J Med Chem 41:428–436
  • 12. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd ed. Academic Press, New York
  • 13. Rolfes J, Andersson JT (1996) Determination of trace amounts of alcohols and phenols in complex mixtures as ferrocenecarboxylic acid esters with gas chromatographyatomic emission detection. Anal Commun 33:429–432
  • 14. Rolfes J, Andersson JT (2001) Determination of alkylphenols after derivatization to ferrocenecarboxylic acid esters with gas chromatography-atomic emission detection. Anal Chem 73:3073–3082
  • 15. Saidi M, Kothari K, Pillai MRA et al. (2001) Cyclopentadienyl technetium tricarbonyl piperidine conjugates: synthesis, biodistribution and imaging studies. J Labelled Compd Radiopharm 44:603–618
  • 16. Saidi M, Seifert S, Kretzschmar M, Bergmann R, Pietzsch HJ (2004) Cyclopentadienyl tricarbonyl complexes of 99mTc for the in vivo imaging of the serotonin 5-HT1A receptor in the brain. J Organ Chem 689:4739–4744
  • 17. Van de Waterbeemd H, Mannhold R (1996) Calculation programs for log P values. Quant Struct Act Relat 15:410–412
  • 18.Wenzel M, Saidi M (1993) Ester der [99]Tc-markieten cytectren-carbonsäure mit alkoholen cyclischer amine als gehirn-affine radiodiagnostika. J Labelled Compd Radiopharm 33:77–80
Typ dokumentu
Bibliografia
Identyfikator YADDA
bwmeta1.element.baztech-article-BUJ6-0023-0028
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