Synthesis and biodistribution of [99mTc]-N-[4-nitro-3-trifluoromethyl-phenyl] cyclopentadienyltricarbonyltechnetium carboxamide, a nonsteroidal antiandrogen flutamide derivative.
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(99m)Tc), an analog of the AR antagonist ligand flutamide. NF(99m)Tc was obtained in 82% yield from the reaction of N-[4-nitro-3-trifluoromethyl-phenyl]-ferrocenecarboxamide (NFFe) with fac-[(99m)Tc(H(2)O)(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 NF(99m)Tc 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.
Laboratoire des Radiopharmaceutiques, Centre National des Sciences et Technologies Nucléaires, Technopôle de Sidi Thabet, 2020, Sidi Thabet, Tunisie.
Tesnim
T
Dallagi
Siden
S
Top
Stéphane
S
Masi
Gérard
G
Jaouen
Mouldi
M
Saidi
D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005485:Flutamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
C556150:(99mTc)-N-(4-nitro-3-trifluoromethylphenyl)cyclopentadienyltricarbonyltechnetium carboxamide; D000726:Androgen Antagonists; D015609:Organotechnetium Compounds; D012997:Solvents; D005485:Flutamide