Development of [F-18]fluorine-substituted Tanaproget as a progesterone receptor imaging agent for positron emission tomography

Bioconjug Chem. 2010 Jun 16;21(6):1096-104. doi: 10.1021/bc1001054.

Abstract

The level of progesterone receptors (PRs) in breast tumors can be used to guide the selection of endocrine therapies for breast cancer patients. To this end, we have prepared a fluorine-18 labeled analogue of Tanaproget, a nonsteroidal progestin with very high PR binding affinity and low affinity for androgen and glucocorticoid receptors, and have studied its tissue distribution in estrogen-primed rats to evaluate its potential for imaging PR levels by positron emission tomography. 4-[(18)F]Fluoropropyl-Tanaproget ([(18)F]9, FPTP) was prepared in three steps, within 140 min at an overall decay-corrected yield of 5% and effective specific activity of >550 Ci/mmol. In biodistribution studies, [(18)F]9 uptake was high in target tissues at both 1 and 3 h (uterus, 4.55 and 5.26%ID/g; ovary, 2.32 and 2.20%ID/g, respectively) and was cleanly blocked by coinjection of excess unlabeled compound. Uterus to blood and muscle activity ratios were 9.2 and 5.2 at 1 h and 32 and 26 at 3 h, respectively. The biodistribution of [(18)F]9 compares favorably to that of previously prepared F-18 labeled steroidal progestins, FENP and FFNP. Its high target tissue uptake efficiency and selectivity, and prolonged retention, suggest that it has excellent promise as a PET imaging agent for PR-positive breast tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzoxazines / chemistry*
  • Binding Sites
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / metabolism*
  • Estrogens / pharmacology
  • Female
  • Fluorine Radioisotopes* / chemistry
  • Ovary / blood supply
  • Ovary / metabolism
  • Ovary / pathology
  • Positron-Emission Tomography / methods*
  • Rats
  • Receptors, Progesterone / analysis*
  • Receptors, Progesterone / metabolism
  • Stimulation, Chemical
  • Thiones / chemistry*
  • Time Factors
  • Tissue Distribution
  • Uterus / blood supply
  • Uterus / metabolism
  • Uterus / pathology

Substances

  • Benzoxazines
  • Estrogens
  • Fluorine Radioisotopes
  • Receptors, Progesterone
  • Thiones
  • tanaproget