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

Journal of Nuclear Medicine

Michael E. Phelps¹  Dale O. Kiesewetter¹  Johannes Czernin¹  Amanda L. Kesner¹  Mark D. Pegram¹  Wei-Ann Hsueh¹  Allison Townsend¹  Malgorzata Beryt¹  Anne Gangloff¹  Betty S. Pio¹  Daniel H.S. Silverman¹ 

关键词: breast cancer;    paclitaxel;    ¹⁸F;    PET;    microPET;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 γ-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.

【 授权许可】

Unknown