Investigating the Vascular Phenotype of Subcutaneously and Orthotopically Propagated PC3 Prostate Cancer Xenografts Using Combined Carbogen Ultrasmall Superparamagnetic Iron Oxide MRI.
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Date
2016-10-01Author
Burrell, JS
Walker-Samuel, S
Boult, JKR
Baker, LCJ
Jamin, Y
Halliday, J
Waterton, JC
Robinson, SP
Type
Journal Article
Metadata
Show full item recordAbstract
The aim of this study was to use the combined carbogen-ultrasmall superparamagnetic iron oxide (CUSPIO) magnetic resonance imaging (MRI) method, which uses spatial correlations in independent susceptibility imaging biomarkers, to investigate and compare the impact of tumor size and anatomical site on vascular structure and function in vivo. Mice bearing either subcutaneous or orthotopic PC3 LN3 prostate tumors were imaged at 7 T, using a multi-gradient echo sequence to quantify R2, before and during carbogen (95% O2/5% CO2) breathing, and subsequently following intravenous administration of USPIO particles. Carbogen and USPIO-induced changes in R2 were used to inform on hemodynamic vasculature and fractional blood volume (%), respectively. The CUSPIO imaging data were also segmented to identify and assess five categories of R2 response. Small and large subcutaneous and orthotopic tumor cohorts all exhibited significantly (P < 0.05) different median baseline R2, ΔR2carbogen, and fractional blood volume. CUSPIO imaging showed that small subcutaneous tumors predominantly exhibited a negative ΔR2carbogen followed by a positive ΔR2USPIO, consistent with a well perfused tumor vasculature. Large subcutaneous tumors exhibited a small positive ΔR2carbogen and relatively low fractional blood volume, suggesting less functional vasculature. Orthotopic tumors revealed a large, positive ΔR2carbogen, consistent with vascular steal, and which may indicate that vascular function is more dependent on site of implantation than tumor size. Regions exhibiting significant ΔR2carbogen, but no significant ΔR2USPIO, suggesting transient vascular shutdown over the experimental timecourse, were apparent in all 3 cohorts. CUSPIO imaging can inform on efficient drug delivery via functional vasculature in vivo, and on appropriate tumor model selection for pre-clinical therapy trials.
Collections
Subject
Cell Line, Tumor
Animals
Humans
Prostatic Neoplasms
Disease Models, Animal
Neovascularization, Pathologic
Carbon Dioxide
Oxygen
Ferric Compounds
Magnetic Resonance Imaging
Particle Size
Male
Magnetite Nanoparticles
Heterografts
Research team
Pre-Clinical MRI
Language
eng
Date accepted
2016-08-01
License start date
2016-10
Citation
Topics in magnetic resonance imaging : TMRI, 2016, 25 (5), pp. 237 - 243
Publisher
Ovid Technologies (Wolters Kluwer Health)