Synthesis and biodistribution of [99mTc]-N-[4-nitro-3-trifluoromethyl-phenyl] cyclopentadienyltricarbonyltechnetium carboxamide, a nonsteroidal antiandrogen flutamide derivative

Abstract

In our efforts to develop a novel class of SPECT imaging agents based on nonsteroidal androgen receptor (AR) antagonists, we have synthesized N-cyclopentadienyltricarbonyltechnetium-N-[4-nitro-3-trifluoromethyl-phenyl] carboxamide (NF^99mTc), an analog of the AR antagonist ligand flutamide. NF^99mTc was obtained in 82% yield from the reaction of N-[4-nitro-3-trifluoromethyl-phenyl]-ferrocenecarboxamide (NFFe) with fac-[^99mTc(H₂O)₃(CO)₃]⁺ in DMF–water at pH 1 and at 150 °C for 1 h. The corresponding Re analog was also prepared. In vitroassays demonstrated high stability of NF^99mTc under physiological conditions, buffer and blood. The tissue biodistribution in mature male Wistar rats showed a significant selective uptake by prostate but this uptake was not blocked by an excess of testosterone acetate. A higher uptake by lung tissues was observed.