title: Assessment of progesterone receptors in breast carcinoma by PET with 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione.
abstract: This first-in-human study was designed to evaluate the safety and dosimetry of the progesterone analog 21-(18)F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione ((18)F-FFNP), as well the feasibility of imaging tumor progesterone receptors (PRs) by PET in breast cancer.
  
  
  METHODS
  Women with breast cancer underwent PET with (18)F-FFNP. Tumor (18)F-FFNP uptake was assessed semiquantitatively by determining maximum standardized uptake value and tumor-to-normal breast (T/N) activity ratio and by Logan graphical analysis. The PET results were correlated with estrogen receptor (ER) and PR status, assessed by in vitro assays of the tumor tissue. The biodistribution of (18)F-FFNP was measured in patients by whole-body PET, and human dosimetry was estimated.
  
  
  RESULTS
  Twenty patients with 22 primary breast cancers (16 PR-positive [PR+] and 6 PR-negative [PR-]) were evaluated. Tumor maximum standardized uptake value was not significantly different in PR+ and PR- cancers (mean ± SD, 2.5 ± 0.9 vs. 2.0 ± 1.3, P = 0.386), but the T/N ratio was significantly greater in the PR+ cancers (2.6 ± 0.9 vs. 1.5 ± 0.3, P = 0.001). In addition, there was a significant correlation between distribution volume ratio and T/N ratio (r = 0.89; P = 0.001) but not between distribution volume ratio and either PR status or standardized uptake value, likely because of small sample size. On the basis of whole-body PET data in 12 patients, the gallbladder appeared to be the dose-limiting organ, with an average radiation dose of 0.113 mGy/MBq. The whole-body dose was 0.015 mGy/MBq, and the effective dose was 0.020 mSv/MBq. No adverse effects of (18)F-FFNP were encountered.
  
  
  CONCLUSIONS
  (18)F-FFNP PET is a safe, noninvasive means for evaluating tumor PRs in vivo in patients with breast cancer. The relatively small absorbed doses to normal organs allow for the safe injection of up to 440 MBq of (18)F-FFNP.
authors.affiliation: Divisions of Nuclear Medicine and Radiological Sciences, Edward Mallinckrodt Institute of Radiology, St. Louis, MO, USA. dehdashtif@mir.wustl.edu
authors.forename: Farrokh
authors.initials: F
authors.lastname: Dehdashti
authors.forename: Richard
authors.initials: R
authors.lastname: Laforest
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Aft
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Dence
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.forename: Kooresh I
authors.initials: KI
authors.lastname: Shoghi
authors.forename: Barry A
authors.initials: BA
authors.lastname: Siegel
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008875:Middle Aged; D009652:Norpregnenes / Q000009:adverse effects / Q000138:chemical synthesis; D049268:Positron-Emission Tomography / Q000379:methods; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000138:chemical synthesis; D011980:Receptors, Progesterone / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: C470081:16,17-((1'-furylmethylidene)dioxy)-21(fluoro)-oxy-19-norpregn-4-ene-3,20-dione; D009652:Norpregnenes; D019275:Radiopharmaceuticals; D011980:Receptors, Progesterone