Human Dosimetry and Preliminary Tumor Distribution of (superscript)18F-Fluoropaclitaxel in Healthy Volunteers and Newly Diagnosed Breast Cancer Patients Using PET/CT
{sup 18}F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used chemotherapy agent. Preclinical data suggest that {sup 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, {sup 18}F-fluoropaclitaxel may also be useful in identifying multidrug resistance and predicting tumor response for drugs other than paclitaxel. 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 {sup 18}F-fluoropaclitaxel and then underwent PET/CT. Healthy volunteers underwent serial whole-body imaging over an approximately 3-h interval, and organ {sup 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. Dosimetry calculations showed that the gallbladder received the highest dose (229.50 {mu}Gy/MBq [0.849 rad/mCi]), followed by the small and large intestines (161.26 {mu}Gy/MBq [0.597 rad/mCi] and 184.59 {mu}Gy/MBq [0.683 rad/mCi]). The resultant effective dose was 28.79 {mu}Gy/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 {sup 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. This study demonstrates the feasibility of using {sup 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 {sup 18}F-fluoropaclitaxel distribution can serve as a surrogate for paclitaxel, and potentially other chemotherapeutic agent retention, in solid tumors.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). Accelerator Test Facility
- Sponsoring Organization:
- USDOE SC OFFICE OF SCIENCE (SC)
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1040534
- Report Number(s):
- BNL-96458-2011-JA; JNMEAQ; TRN: US1202488
- Journal Information:
- Journal of Nuclear Medicine, Vol. 52, Issue 9; ISSN 0161-5505
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BILIARY TRACT
CHEMOTHERAPY
DISTRIBUTION
DOSIMETRY
INFUSION
LABELLED COMPOUNDS
LARGE INTESTINE
MAMMARY GLANDS
NEOPLASMS
ORGANS
PATIENTS
RADIATION DOSES
RADIOPHARMACEUTICALS
RETENTION
SUBSTRATES
18F-Fluoropaclitaxel (FPAC)
multidrug resistance (MDR)
PET/CT imaging
paclitaxel
dosimetry
breast cancer
positron emission tomography (PET)
computed tomography (CT)
accelerator test facility