Human Dosimetry and Preliminary Tumor Distribution of 18F-Fluoropaclitaxel in Healthy Volunteers and Newly Diagnosed Breast Cancer Patients Using PET/CT

Journal of Nuclear Medicine

Jean Logan¹  Jerry I. Hirsch¹  James McCumisky¹  Kathy Moorman-Sykes¹  Harry D. Bear¹  Joseph D. Kalen¹  John D. Wilson¹  Peter L. Choyke¹  Stephen Adler¹  Karen A. Kurdziel¹ 

关键词: ¹⁸F-fluoropaclitaxel (FPAC);    multidrug resistance (MDR);    PET/CT imaging;    paclitaxel;    dosimetry;    breast cancer;   

DOI  :  10.2967/jnumed.111.091587

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

18F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used chemotherapy agent. Preclinical data suggest that 18F-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, 18F-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 18F-fluoropaclitaxel and then underwent PET/CT. Healthy volunteers underwent serial whole-body imaging over an approximately 3-h interval, and organ 18F 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 18F-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 18F-fluoropaclitaxel PET/CT tumor imaging and provides radiation dosimetry measurements in humans. Although further study is needed, it is hoped that the measured intratumoral 18F-fluoropaclitaxel distribution can serve as a surrogate for paclitaxel, and potentially other chemotherapeutic agent retention, in solid tumors.

【 授权许可】

Unknown