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.

Conclusion: (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.

Conflict of interest statement

No other potential conflict of interest relevant to this article was reported.

Figures

FIGURE 1

Representative transverse 18F-FFNP PET images in patient with PR+ breast cancer (A) and another with PR− breast cancer (B). Arrows point to tumor.

FIGURE 2

18F-FFNP uptake assessed by SUVmax (left) and T/N ratio (right) in PR+ and PR− breast cancers.

FIGURE 3

Time−activity distribution in liver, tumor, normal breast, and blood (from ventricular chamber). Data were normalized for 370-MBq injection (patient 5, dynamic cohort) with ER+ and PR+ tumor. Uptake of 18F-FFNP in this patient’s tumor was twice that in her normal breast.

FIGURE 4

Typical whole-body coronal images of patient at 1 h (A) and 2 h (B) after injection of 370 MBq (10 mCi) of 18F-FFNP. Accumulation of activity is primarily seen in liver and small intestines

FIGURE 5

Sagittal 18F-FFNP images registered to CT images showing accumulation in liver, intestines, uterus, and urinary bladder.