title: Tumor perfusion imaging predicts the intra-tumoral accumulation of liposomes.
abstract: Liposomes have proven to be a viable drug delivery strategy resulting in significant increases in tumor accumulation of drugs via exploitation of the enhanced permeability and retention (EPR) effect. However, significant variability has been observed in their bulk tumor accumulation and intra-tumoral distribution. The heterogeneous accumulation of liposomes in solid tumors is largely believed to result from the chaotic morphology and physiology of tumor blood vessels. Thus, tumor perfusion imaging may provide a novel method to predict the accumulation and resulting therapeutic effect of liposome formulations. In this study, dynamic contrast enhanced computed tomography (DCE-CT) was employed to quantitatively estimate the intra-tumoral distribution of perfusion and anatomical CT was used to map the spatio-temporal accumulation of a CT-liposome contrast agent. A statistically significant positive correlation was found between quantitative and semi-quantitative measures of tumor perfusion (i.e. K(trans), vp, and AUC(iox)) and liposome accumulation (AUC(lipo) and C(peak)) in two mouse xenograft models of human cervical cancer. Specifically, it was found that regions with higher K(trans),vp, and AUC(iox) had greater liposome accumulation. These findings demonstrate that DCE-CT measurements of tumor perfusion may be an important technique for selecting patients that are likely to respond to liposome and potentially other nanoparticle-based therapies.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada. Electronic address: shawn.stapleton@rmp.uhn.on.ca.
authors.forename: Shawn
authors.initials: S
authors.lastname: Stapleton
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Allen
authors.affiliation: Biostatistics, Princess Margaret Cancer Centre, Toronto, Canada.
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.affiliation: TECHNA Institute and Ontario Cancer Institute, University Health Network, Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada; Departments of Radiation Oncology, Medical Biophysics, and IBBME, University of Toronto, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Jaffray
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000098:blood supply / Q000000981:diagnostic imaging; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008081:Liposomes / Q000097:blood / Q000493:pharmacokinetics*; D051379:Mice; D055420:Perfusion Imaging; D014055:Tomography, Emission-Computed; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D008081:Liposomes
keywords: Dynamic contrast enhanced computed tomography; Image guided drug delivery; Liposomes; Microcirculation; Tumor blood flow