title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research/National Cancer Institute/National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Kurdziel
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Kalen
authors.forename: Jerry I
authors.initials: JI
authors.lastname: Hirsch
authors.forename: John D
authors.initials: JD
authors.lastname: Wilson
authors.forename: Harry D
authors.initials: HD
authors.lastname: Bear
authors.forename: Jean
authors.initials: J
authors.lastname: Logan
authors.forename: James
authors.initials: J
authors.lastname: McCumisky
authors.forename: Kathy
authors.initials: K
authors.lastname: Moorman-Sykes
authors.forename: Stephen
authors.initials: S
authors.lastname: Adler
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D008297:Male; D009928:Organ Specificity; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019275:Radiopharmaceuticals; C526531:4-fluoropaclitaxel; D017239:Paclitaxel