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Predicting Chemotherapy Response to Paclitaxel with ¹⁸F-Fluoropaclitaxel and PET

¹ Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California; and ² Divison of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California

Correspondence: For correspondence or reprints contact: Daniel H.S. Silverman, MD, PhD, CHS AR-144, Nuclear Medicine Clinic, MC694215, UCLA Medical Center, Los Angeles, CA 90095-6942. E-mail: dsilver{at}ucla.edu Guest Editor: Norbert Avril, St. Bartholomew's Hospital

Paclitaxel is used as a chemotherapy drug for the treatment of various malignancies, including breast, ovarian, and lung cancers. To evaluate the potential of a noninvasive prognostic tool for specifically predicting the resistance of tumors to paclitaxel therapy, we examined the tumoral uptake of ¹⁸F-fluoropaclitaxel (¹⁸F-FPAC) in mice bearing human breast cancer xenografts by using small-animal–dedicated PET and compared ¹⁸F-FPAC uptake with the tumor response to paclitaxel treatment. Methods: PET data were acquired after tail vein injection of approximately 9 MBq of ¹⁸F-FPAC in anesthetized nude mice bearing breast cancer xenografts. Tracer uptake in reconstructed images was quantified by region-of-interest analyses and compared with the tumor response, as measured by changes in tumor volume, after treatment with paclitaxel. Results: Mice with tumors that progressed demonstrated lower tumoral uptake of ¹⁸F-FPAC than mice with tumors that did not progress or that regressed (r = 0.55, P < 0.02; n = 19), indicating that low ¹⁸F-FPAC uptake was a significant predictor of chemoresistance. Conversely, high ¹⁸F-FPAC uptake predicted tumor regression. This relationship was found for mice bearing xenografts from cell lines selected to be either sensitive or intrinsically resistant to paclitaxel in vitro. Conclusion: PET data acquired with ¹⁸F-FPAC suggest that this tracer holds promise for the noninvasive quantification of its distribution in vivo in a straightforward manner. In combination with approaches for examining other aspects of resistance, such quantification could prove useful in helping to predict subsequent resistance to paclitaxel chemotherapy of breast cancer.

Key Words: breast cancer • paclitaxel • ¹⁸F • PET • chemotherapy

COPYRIGHT © 2006 by the Society of Nuclear Medicine, Inc.

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