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

Area of Science:

• Inorganic Chemistry
• Radiochemistry
• Medicinal Chemistry

Background:

• Dihydrobis(azolyl)borate ligands offer unique coordination properties.
• The fac-[99mTc(CO)3]+ core is a crucial component in developing diagnostic radiotracers.

Purpose of the Study:

• To synthesize and characterize a novel dihydrobis(azolyl)borate ligand and its technetium-99m complex.
• To evaluate the stability and potential of the new complex for brain imaging applications.

Main Methods:

• Synthesis of Na[H2B(tim(Me))(3,5-Me2pz)] (L1) and fac-[99mTc(κ(3)-H(μ-H)B(tim(Me))(3,5-Me2-pz))(CO)3] (4a).
• Characterization using analytical techniques including X-ray diffraction.
• In vitro stability studies in phosphate-buffered saline (PBS).
• In vivo biodistribution studies in mice.

Main Results:

• Successful synthesis of the novel ligand L1 and its rhenium (4) and technetium-99m (4a) complexes.
• Complex 4a demonstrated high radiochemical purity and stability in vitro.
• The B-H...99mTc bond remained intact under physiological conditions.
• Biodistribution studies confirmed blood-brain barrier penetration of complex 4a.

Conclusions:

• Dihydrobis(azolyl)borate ligands can stabilize the fac-[99mTc(CO)3]+ unit.
• Complex 4a exhibits excellent in vitro stability and crosses the blood-brain barrier.
• This compound represents a promising new platform for developing radiopharmaceuticals for brain imaging.