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Synthesis and biological evaluation of tricarbonyl Re(I) and Tc(I) complexes anchored by poly(azolyl)borates: application on the design of radiopharmaceuticals for the targeting of 5-HT1A receptors

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Abstract

The building blocks fac-[99mTc{κ3-HB(timMe)3}(CO)3] and fac-[99mTc{κ3-R(μ-H)B(timMe)2}(CO)3] [R is H (4a), Ph (5a); timMe is 2-mercapto-1-methylimidazolyl] were obtained almost quantitatively by reacting fac-[99mTc(CO)3(H2O)3]+ with the corresponding scorpionate. These compounds cross the intact blood–brain barrier in mice, with significant retention in the case of 4a and 5a. Using 4a as the lead structure, we have synthesized the functionalized complexes fac-[M{κ3-H(μ-H)B(timBu-pip)2}(CO)3] [M is Re (8), 99mTc (8a); timBu-pip is methyl[4-((2-methoxyphenyl)-1-piperazinyl)butyl](2-mercapto-1-methylimidazol-5-yl)methanamide] and fac-[M{κ 3-H(μ-H)B(timMe)(timBu-pip)}(CO)3] [M is Re (9), 99mTc (9a)] and evaluated their potential as radioactive probes for the targeting of brain 5-HT1A serotonergic receptors. The Re complexes exhibit excellent affinity [IC50=0.172 ± 0.003 nM (8); IC50=0.65 ± 0.01 nM (9)] for the 5-HT1A receptor. The radioactive congeners (99mTc) have shown an initial brain uptake of 1.38 ± 0.46%ID g−1 (8a) and 0.43 ± 0.12%ID g−1 (9a), but suffer from a relatively fast washout.

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Acknowledgements

This work was partially supported by the FCT (POCTI/QUI/42939/2001). We thank Mallinkrodt-Tyco for financial support. R.G. and L.M. would like to thank the Fundação para a Ciência e Tecnologia (National Foundation for Science and Technology) for Ph.D. and postdoctoral research grants, respectively. We wish to acknowledge Ana Coelho from the Laboratório de Espectrometria de Massa at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Portugal, for the ESI–MS analysis.

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Authors and Affiliations

  1. Departamento de Química, ITN, Estrada Nacional 10, 2686-953, Sacavém Codex, Portugal

    Raquel Garcia, Lurdes Gano, Leonor Maria, António Paulo & Isabel Santos

  2. Institute of Bioinorganic and Radiopharmaceutical Chemistry, Forschungszentrum Rossendorf, 01314, Dresden, Germany

    Hartmut Spies

Authors
  1. Raquel Garcia
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  2. Lurdes Gano
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  3. Leonor Maria
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  4. António Paulo
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Correspondence to Isabel Santos.

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Garcia, R., Gano, L., Maria, L. et al. Synthesis and biological evaluation of tricarbonyl Re(I) and Tc(I) complexes anchored by poly(azolyl)borates: application on the design of radiopharmaceuticals for the targeting of 5-HT1A receptors. J Biol Inorg Chem 11, 769–782 (2006). https://doi.org/10.1007/s00775-006-0124-7

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  • DOI: https://doi.org/10.1007/s00775-006-0124-7

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