title: Development of [F-18]fluorine-substituted Tanaproget as a progesterone receptor imaging agent for positron emission tomography.
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.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, 61801, USA.
authors.forename: Jae Hak
authors.initials: JH
authors.lastname: Lee
authors.forename: Hai-bing
authors.initials: HB
authors.lastname: Zhou
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Dence
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Carlson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000737:chemistry*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D010053:Ovary / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D011980:Receptors, Progesterone / Q000032:analysis* / Q000378:metabolism; D013268:Stimulation, Chemical; D013871:Thiones / Q000737:chemistry*; D013997:Time Factors; D014018:Tissue Distribution; D014599:Uterus / Q000098:blood supply / Q000378:metabolism / Q000473:pathology
chemical_list: D048588:Benzoxazines; D004967:Estrogens; D005462:Fluorine Radioisotopes; D011980:Receptors, Progesterone; D013871:Thiones; C504446:tanaproget