Molecular Imaging Program, Center for Cancer Research/National Cancer Institute/National Institutes of Health, Bethesda, Maryland 20892, USA.
J Nucl Med. 2011 Sep;52(9):1339-45. doi: 10.2967/jnumed.111.091587. Epub 2011 Aug 17.
(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.
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.
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.
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.
（18）F-氟紫杉醇是紫杉醇的一种放射性标记形式，紫杉醇是一种广泛应用的化疗药物。临床前数据表明，（18）F-氟紫杉醇可能是测量紫杉醇摄取的合理替代物。作为与多药耐药相关的药物外排泵 P-糖蛋白的底物，（18）F-氟紫杉醇也可能有助于识别多药耐药，并预测除紫杉醇以外的其他药物的肿瘤反应。
在获得知情同意后，3 名健康志愿者和 3 名未经治疗的乳腺癌患者（新辅助化疗候选者，肿瘤大小>2cm）接受静脉输注（18）F-氟紫杉醇，然后进行 PET/CT 检查。健康志愿者在大约 3 小时的时间间隔内进行全身连续成像，通过未校正衰减的时间-活性曲线确定器官（18）F 居留时间，以确定剂量测定。使用 OLINDA/EXM 软件计算辐射剂量估算值。对于乳腺癌患者，对原发肿瘤进行 60 分钟的动态成像，然后在注射后 1 小时和 2 小时进行全身静态扫描。
剂量测定计算显示，胆囊接受的剂量最高（229.50μGy/MBq[0.849rad/mCi]），其次是小肠和大肠（161.26μGy/MBq[0.597rad/mCi]和 184.59μGy/MBq[0.683rad/mCi]）。所得有效剂量为 28.79μGy/MBq（0.107rem/mCi）。在注射后约 1 小时，衰变校正后活动的平均 42%在胃肠道系统中，肿瘤中的平均 0.01%。所有 3 名乳腺癌患者均显示（18）F-氟紫杉醇的保留，并最终在包括紫杉醇（紫杉醇或多西紫杉醇）在内的化疗后表现出完全病理反应（乳房或腋窝淋巴结中无浸润性癌）在手术切除时。肿瘤与背景的比值随时间增加，在 20 分钟时最大增加到 7.7。
本研究证明了使用（18）F-氟紫杉醇 PET/CT 肿瘤成像的可行性，并提供了人体辐射剂量测定值。尽管还需要进一步研究，但希望测量的肿瘤内（18）F-氟紫杉醇分布可以作为紫杉醇的替代物，并且可能作为其他化学治疗药物在实体肿瘤中的保留物。
