Synthesis and biological evaluation of 7alpha Re/Tc "3+1" and cyclopentadienyltri- carbonylmetal (CpTM) estrogen mimics based on the conjugated design


Synthesis and biological evaluation of 7alpha Re/Tc "3+1" and cyclopentadienyltri- carbonylmetal (CpTM) estrogen mimics based on the conjugated design

Skaddan, M. B.; Wüst, F.; Welch, M. J.; Katzenellenbogen, J. A.

The diagnosis and staging of breast cancer could be improved by the development of imaging radiopharmaceuticals that provide a non-invasive determination of the estrogen receptor (ER) status of tumor cells. Towards this goal, we have synthesized a number of Re and Tc-labeled estradiol (1) mimics based on the conjugated design, which tethers a metal-containing moiety to an existing steroid. In this study, the 7alpha position of estradiol was chosen as the tether site, due to its well known
tolerance of bulky substituents. 1 The metal was stabilized using either the "3+1" design (2,3), or the cyclopentadienyltricarbonylmetal (CpTM) approach (4,5,6) . In the "3+1" design, a tridentate ligand and a monodentate ligand surround an oxometal core.2 In the CpTM design, a substituted Cp and three carbonyls are coordinated to a Re/Tc(I) center.3,4
The advantages of using the "3+1" and CpTM desings are the well-established stability of both systems, as well as the ability to produce both systems efficiently at the tracer level.2,4
The first tether used was a hexyl spacer, and the synthesis of the precursors for targets 2-6 started with THP-protected estradiol 7 (Scheme 1). After oxidation to ketone 8 using a previously published method, standard alkylation conditions introduced the hexene side chain to form 9 , with BEt3 as an additive to stabilize the enolate and prevent O-alkylation.

Keywords: estrogen; radiotracers; rhenium; technetium

  • Lecture (Conference)
    13th International symposium on Radiopharmaceutical Chemistry, St. Louis, USA 27.6.-1.7.99
  • Abstract in refereed journal
    J. Labelled Cpd. Radiopharm. 42 (Suppl.1) (1999) S153-S155

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Publ.-Id: 2084