title: Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors.
abstract: The heterogeneous intra-tumoral accumulation of liposomes is a critical determinant of their efficacy. Both the chaotic tumor microcirculation and elevated IFP are linked to the heterogeneous intra-tumoral distribution of nanotechnology-based drug delivery systems such as liposomes. In the present study, the relationship between tumor microcirculation, elevated IFP, and accumulation of nanoparticles was investigated through in vivo experimentation. This was accomplished by evaluation of the tumor microcirculation using dynamic contrast enhanced computed tomography (DCE-CT) and measurement of tumor IFP using a novel image-guided robotic needle placement system connected to the micro-CT scanner. The intra-tumoral accumulation of liposomes was determined by CT image-based assessment of a nanoparticle liposomal formulation that stably encapsulate the contrast agent iohexol (CT-liposomes). CT imaging allowed for co-localization of the spatial distribution of tumor hemodynamics, IFP and CT-liposome accumulation in an individual subcutaneous xenograft mouse model of breast cancer. Measurements led to the discovery that perfusion and plasma volume fraction are strong mediators of the intra-tumoral distribution of liposomes. Furthermore, the results suggest that IFP plays an indirect role in mediating liposome distribution through modulating blood flow.
authors: Department of Medical Biophysics, University of Toronto; Leslie Dan Faculty of Pharmacy, University of Toronto; STTARR Innovation Centre, Princess Margaret Cancer Centre; Shawn.Stapleton@rmp.uhn.ca.
authors: Shawn
authors: S
authors: Stapleton
authors: Leslie Dan Faculty of Pharmacy, University of Toronto.
authors: Daniel
authors: D
authors: Mirmilshteyn
authors: STTARR Innovation Centre, Princess Margaret Cancer Centre; Institute of Biomaterials and Biomedical Engineering, University of Toronto.
authors: Jinzi
authors: J
authors: Zheng
authors: Leslie Dan Faculty of Pharmacy, University of Toronto; Institute of Biomaterials and Biomedical Engineering, University of Toronto; Techna Institute, University Health Network.
authors: Christine
authors: C
authors: Allen
authors: Department of Medical Biophysics, University of Toronto; Leslie Dan Faculty of Pharmacy, University of Toronto; STTARR Innovation Centre, Princess Margaret Cancer Centre; Institute of Biomaterials and Biomedical Engineering, University of Toronto; Techna Institute, University Health Network; Radiation Medicine Program, Princess Margaret Cancer Centre.
authors: David A
authors: DA
authors: Jaffray
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D003287:Contrast Media; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D051379:Mice; D010477:Perfusion; D011312:Pressure; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D003287:Contrast Media; D008081:Liposomes