A novel 99mTc-labeled testosterone derivative as a potential agent for targeting androgen receptors.
With an insight that ligands possessing a N2S2 tetradentate array of donor atoms serve as ideal bifunctional chelating agents (BFCA) in the radiolabeling of target-specific agents, 5-hydroxy-3,7-diazanonan-1,9-dithiol (DAHPES) with a derivatizable substituent in the form of a hydroxyl group in the backbone was synthesized. The preparation of a steroid conjugate via coupling of this BFCA with testosterone-3-(O-carboxymethyl) oxime and the subsequent radiolabeling of the conjugate under optimized conditions with 99mTc, the ideal diagnostic radionuclide in nuclear medicine procedures, are reported. The immunoreactivity of the radiolabeled conjugate was demonstrated in a study using anti-testosterone antibodies, wherein the radiolabeled conjugate exhibited significant binding with antiserum to testosterone. Cell-uptake studies in DU145 prostate carcinoma cell line bearing androgen receptors (ARs) and comparison with AR non-bearing breast carcinoma cell line revealed the specific binding of the steroidal moiety with the testosterone receptor.
Das
Tapas
T
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
Banerjee
Sharmila
S
Samuel
Grace
G
Bapat
Ketaki
K
Subramanian
Suresh
S
Pillai
Maroor R A
MR
Venkatesh
Meera
M
D000726:Androgen Antagonists / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000494:pharmacology*; D013667:Technetium / Q000737:chemistry*; D013739:Testosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D008024:Ligands; D019275:Radiopharmaceuticals; D013739:Testosterone; D013667:Technetium