Human dosimetry and preliminary tumor distribution of 18F-fluoropaclitaxel in healthy volunteers and newly diagnosed breast cancer patients using PET/CT

Abstract

(18)F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used chemotherapy agent. Preclinical data suggest that (18)F-fluoropaclitaxel may be a reasonable surrogate for measuring the uptake of paclitaxel. As a substrate of P-glycoprotein, a drug efflux pump associated with multidrug resistance, (18)F-fluoropaclitaxel may also be useful in identifying multidrug resistance and predicting tumor response for drugs other than paclitaxel.

Methods: After informed consent was obtained, 3 healthy volunteers and 3 patients with untreated breast cancer (neoadjuvant chemotherapy candidates, tumor size > 2 cm) received an intravenous infusion of (18)F-fluoropaclitaxel and then underwent PET/CT. Healthy volunteers underwent serial whole-body imaging over an approximately 3-h interval, and organ (18)F residence times were determined from the time-activity curves uncorrected for decay to determine dosimetry. Radiation dose estimates were calculated using OLINDA/EXM software. For breast cancer patients, dynamic imaging of the primary tumor was performed for 60 min, followed by static whole-body scans at 1 and 2 h after injection.

Results: Dosimetry calculations showed that the gallbladder received the highest dose (229.50 μGy/MBq [0.849 rad/mCi]), followed by the small and large intestines (161.26 μGy/MBq [0.597 rad/mCi] and 184.59 μGy/MBq [0.683 rad/mCi]). The resultant effective dose was 28.79 μGy/MBq (0.107 rem/mCi). At approximately 1 h after injection, an average of 42% of the decay-corrected activity was in the gastrointestinal system, with a mean of 0.01% in the tumor. All 3 breast cancer patients showed retention of (18)F-fluoropaclitaxel and ultimately demonstrated a complete pathologic response (no invasive cancer in the breast or axillary nodes) to chemotherapy that included a taxane (either paclitaxel or docetaxel) at surgical resection. The tumor-to-background ratio increased with time to a maximum of 7.7 at 20 min.

Conclusion: This study demonstrates the feasibility of using (18)F-fluoropaclitaxel PET/CT tumor imaging and provides radiation dosimetry measurements in humans. Although further study is needed, it is hoped that the measured intratumoral (18)F-fluoropaclitaxel distribution can serve as a surrogate for paclitaxel, and potentially other chemotherapeutic agent retention, in solid tumors.

Figures

FIGURE 1

Serial coronal maximum-intensity-projection images of healthy volunteer after left wrist injection of 218.3 MBq (5.9 mCi) of 18F-fluoropaclitaxel.

FIGURE 2

Average time–activity curves for selected solid organs in 3 healthy volunteers. Error bars represent SD.

FIGURE 3

Time–activity curves for tumor SUV (A), tumor to blood pool (B), and tumor to background (C).

FIGURE 4

Graphical analysis of dynamic tumor data for all 3 patients. Slope of linear portion estimates distribution volume ratio of tumor and reference tissue (in this case, contralateral noninvolved breast).

FIGURE 5

Coregistered coronal CT (A), 18F-fluoropaclitaxel (SUVmax, 1.2) (B), and 18F-FDG (SUVmax, 12.0) (C) maximum-intensity-projection images of breast cancer patient with large right confirmed breast tumor (arrow).

FIGURE 6

Breast cancer patient with biopsy-proven tumor in right breast mass (arrows on CT [A] and PET [B and C] scans) and biopsy-proven sarcoid in mediastinum or hila. Increased 18F-fluoropacli-taxel (B; SUV uptake corresponding to tumor and no 18F-fluoropaclitaxel uptake corresponding to mediastinum/hilar lesions) seen on 18F-FDG scan (C; open arrow). 18F-FDG and 18F-fluoropaclitaxel images are scaled to SUVmax of 2.0. Tumor SUVmax on18F-fluoropa-clitaxel (B) at 78 min was 0.9; 18F-FDG (C) SUVmax at 123 min was 10.0. Uptake in anterior portion of left arm on 18F-fluoropaclitaxel image (B) is residual tracer within vessel wall. FPAC 5 fluoropaclitaxel.