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 (NF99mTc), an analog of the AR antagonist ligand flutamide. NF99mTc 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 vitro assays demonstrated high stability of NF99mTc 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. © 2010 The Royal Society of Chemistry.