Synthesis and biodistribution studies of two novel radiolabeled estrone derivatives.
BACKGROUND
Two 99mTc-DTPA attached estrone derivatives were synthesized and their radiopharmaceutical potential was determined using female albino Wistar rats.


METHODS
Two novel radiolabeled estrone derivatives, 99mTc-2,2',2"2"'-(2,2'-(2-(3-methoxy-13-methyl-17-oxo-7, 8, 9, 11, 12, 13, 14, 15, 16, 7-decahydro-6H- cyclopenta[a]phenanthren-2-ylamino)-2- oxoethylazanediyl) bis(ethane-2,1-diyl)) bis(azanetriyl) tetraacetic acid (99mTc-2-DTPA-3-methoxy estrone) and 9mTc-2,2',2",2'"-(2,2'- (2-(3-methoxy-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro- 6H-cyclopenta[a]phenanthren-4-ylamino)-2-oxoethylazanediyl) bis(ethane-2,1-diyl))bis(azanetriyl)tetraacetic acid (99mTc-4-DTPA-3-methoxy estrone) were synthesized starting from estrone (3-hydroxy-13-methyl-7,8, 9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one) and DTPA anhydride (2-(bis(2-(2,6-dioxomorpholino)ethyl)amino)acetic acid) as potential estrogen receptor imaging agents. The products were crystallized in ethyl alcohol (95%), purified by high performance liquid chromatography (HPLC) and characterized by nuclear magnetic resonance (NMR) and infrared spectroscopy (IR). The effect of the radiolabeled compounds on the biological behaviour of the molecules was evaluated through biodistribution studies in female albino Wistar rats. The rats were sacrificed at various time intervals, their organs were removed, and the activities of organs were counted using a gamma counter equipped with a Cd(Te) solid state detector.


CONCLUSIONS
Organ uptake was calculated as activity/gram tissue and time versus activity curves were generated. The tissue distribution studies exhibited a receptor-mediated uptake in the target organs of the rats for each compound. Both 99mTc-2-DTPA-3-methoxy estrone and 99mTc-4-DTPA-3-methoxy estrone were stable in vitro and were mainly excreted through the hepatobiliary pathway. The biological data showed that the 99mTc-2-DTPA-3-methoxy estrone had higher uptake in the target tissues than the 99mTc-4-DTPA-3-methoxy estrone. The favourable in vitro/in vivo stability and biodistribution profiles suggest that these radioligands are good candidates for further exploration of their potential clinical applications.
Enginar
Huseyin
H
Afyon Kocatepe University, Department of Chemistry, Afyon, Turkey.
Unak
Perihan
P
Lambrecht
Fatma Yurt
FY
Biber Muftuler
F Zumrut
FZ
Medine
E Ilker
EI
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004970:Estrone / Q000031:analogs & derivatives / Q000737:chemistry*; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared; D013667:Technetium / Q000737:chemistry*; D016284:Technetium Tc 99m Pentetate / Q000737:chemistry*; D014018:Tissue Distribution
D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D004970:Estrone; D013667:Technetium; D016284:Technetium Tc 99m Pentetate