99mTc(I) scorpionate complexes for brain imaging: synthesis, characterization and biological evaluation

The new dihydrobis(azolyl)borate ligand Na[H2B(tim(Me))(3,5-Me2pz)] (L1) was synthesized and used to prepare the complexes fac-[M(κ(3)-H(μ-H)B(tim(Me))(3,5-Me2-pz))(CO)3] (M = Re (4), 99mTc (4a)). L1 and 4 were characterized by common analytical techniques, including X-ray diffraction analysis for 4. The successful synthesis of complex 4a, obtained with high radiochemical purity, has shown for the first time that dihydrobis(azolyl)borate ligands combining 2- mercaptoimidazolyl and pyrazolyl rings are capable of stabilizing the fac-[99mTc(CO)3]+ unit. Complex 4a displays a high in vitro stability, in PBS (pH 7.4), indicating that the B-H...99mTc bond is retained even under physiological conditions. Biodistribution studies in mice have shown that 4a can cross the blood-brain barrier, emerging as a good alternative for the design of radiopharmaceuticals for brain imaging.