Synthesis and biological evaluation of a novel 99mTc-cyclopentadienyltricarbonyl technetium complex as a new potential brain perfusion imaging agent

摘要

A new cytectrene prototype of general formula RCpTc(CO)₃ (R = C₆H₅NHCO, Cp = cyclopentadienyl moiety) has been synthesized from N-phenylferrocenecarboxamide 2, characterized and evaluated as a potential brain perfusion imaging agent. An improved procedure has been developed to obtain both the ligand 2, characterized by its solid-state structure (orthorhombic, Pccn, a = 10.4443(2) ?, b = 26.1467(6) ?, c = 9.9977(3) ?), and the corresponding metallic Tc- and Re-complexes in good yield. These latter complexes possessed similar HPLC retention times, thereby indicating identity of their molecular structures. The Tc-complex 99mTc-2 is lipophilic enough to cross the blood-brain barrier. This complex exhibits good brain uptake (1.41% injected dose per gram tissue at 5 min) combined with a fairly good retention of radioactivity in brain (0.48% injected dose per gram tissue after 1 h). Then, the distribution of the activity at 5 min post-injection in various rat brain regions showed a higher accumulation in the hippocampus area. The new 99mTc-cyclopentadienyltricarbonyl technetium complex reported here showed promising biological results, making it an interesting base for the development of a new generation of cytectrene as brain perfusion imaging agent. Copyright ? 2011 John Wiley & Sons, Ltd.