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Estimation of Paclitaxel Biodistribution and Uptake in Human-Derived Xenografts In Vivo with ¹⁸F-Fluoropaclitaxel

¹ Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California
² Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland
³ Divison of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California

Paclitaxel (PAC) is widely used as a chemotherapy drug in the treatment of various malignancies, including breast, ovarian, and lung cancers. We examined the biodistribution of ¹⁸F-fluoropaclitaxel (¹⁸F-FPAC) in mice with and without human breast cancer tumor xenografts by use of small-animal–dedicated PET (microPET) and clinically practical semiquantitative methods. We compared the PET data to data derived from direct harvesting and analysis of blood, organs, and breast carcinoma xenografts. Methods: PET data were acquired after tail vein injection of ¹⁸F-FPAC in nude mice. Tracer biodistribution in reconstructed images was quantified by region-of-interest analysis. Biodistribution also was assessed by harvesting and analysis of dissected organs, tumors, and blood after coadministration of ¹⁸F-FPAC and ³H-PAC. ¹⁸F content in each tissue was assessed with a -well counter, and ³H content was quantified by scintillation counting of solubilized tissue after ¹⁸F radioactive decay. Results: The distributions of ¹⁸F-FPAC and ³H-PAC were very similar, with the highest concentrations in the small intestine, the lowest concentrations in the brain, and intermediate concentrations in tumor. Uptake in these and other tissues was not inhibited by the presence of more pharmacologic doses of unlabeled PAC. Administration of the P-glycoprotein modulator cyclosporine doubled the uptake of both ¹⁸F-FPAC and ³H-PAC into tumor. Conclusion: PET studies with ¹⁸F-FPAC can be used in conjunction with clinically practical quantification methods to yield estimates of PAC uptake in breast cancer tumors and normal organs noninvasively.

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

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