UNLABELLED: (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.
UNLABELLED: (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 cancerpatients, 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 3breast cancerpatients 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.
Authors: Wei-Ann Hsueh; Amanda L Kesner; Anne Gangloff; Mark D Pegram; Malgorzata Beryt; Johannes Czernin; Michael E Phelps; Daniel H S Silverman Journal: J Nucl Med Date: 2006-12 Impact factor: 10.057
Authors: Anne Gangloff; Wei-Ann Hsueh; Amanda L Kesner; Dale O Kiesewetter; Betty S Pio; Mark D Pegram; Malgorzata Beryt; Allison Townsend; Johannes Czernin; Michael E Phelps; Daniel H S Silverman Journal: J Nucl Med Date: 2005-11 Impact factor: 10.057
Authors: Dale O Kiesewetter; Elaine M Jagoda; Chih-Hao K Kao; Ying Ma; Laura Ravasi; Kazuaki Shimoji; Lawrence P Szajek; William C Eckelman Journal: Nucl Med Biol Date: 2003-01 Impact factor: 2.408
Authors: Karen A Kurdziel; Dale O Kiesewetter; Richard E Carson; William C Eckelman; Peter Herscovitch Journal: J Nucl Med Date: 2003-08 Impact factor: 10.057
Authors: Iván Peñuelas; Inés Domínguez-Prado; María J García-Velloso; Josep M Martí-Climent; Macarena Rodríguez-Fraile; Carlos Caicedo; María Sánchez-Martínez; José A Richter Journal: J Oncol Date: 2012-08-29 Impact factor: 4.375