| Publication Type |
Journal Article |
| Title |
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 |
| Authors |
Raquel Garcia Lurdes Gano Leonor Maria Antonio Paulo Isabel Santos Hartmut Spies |
| Groups |
IOARC |
| Journal |
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY |
| Year |
2006 |
| Month |
September |
| Volume |
11 |
| Number |
6 |
| Pages |
769-782 |
| Abstract |
The building blocks fac-[Tc-99m\kappa(3)-HB (tim(Me))(3)\(CO)(3)] and fac-[Tc-99m\kappa(3)-R(mu-H)B(tim(Me))(2)\ (CO)(3)] [R is H (4a), Ph (5a); tim(Me) is 2-mercapto-1-methylimidazolyl] were obtained almost quantitatively by reacting fac-[Tc-99m(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\kappa(3) -H(mu-H)B(tim(Bu-pip))(2)\(CO)(3)] [M is Re (8), Tc-99m (8a); tim(Bu-pip) is methyl[4-((2-methoxyphenyl)-1-piper-azinyl)butyl](2-mercapto-1-methyli midazol-5-yl)methan amide] and fac-[M\kappa(3)-H(mu-H)B(tim(Me))(tim(Bu-pip))\ (CO)(3)] [M is Re (9), Tc-99m (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 (Tc-99m) 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. |
| DOI |
http://dx.doi.org/10.1007/s00775-006-0124-7 |
| ISBN |
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| Publisher |
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| Book Title |
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| ISSN |
0949-8257 |
| EISSN |
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| Conference Name |
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| Bibtex ID |
ISI:000239895600010 |
| Observations |
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