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Non‐invasive in vivo imaging of vessel calibre in orthotopic prostate tumour xenografts
Author(s) -
WalkerSamuel Simon,
Boult Jessica K.R.,
McPhail Lesley D.,
Box Gary,
Eccles Suzanne A.,
Robinson Simon P.
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26112
Subject(s) - medicine , in vivo , magnetic resonance imaging , prostate , pathology , perfusion , nuclear medicine , blood vessel , necrosis , radiology , cancer , biology , microbiology and biotechnology
Susceptibility contrast magnetic resonance imaging (MRI), utilising ultrasmall superparamagnetic iron oxide (USPIO) particles, was evaluated for the quantitation of vessel size index ( R v , μm), a weighted average measure of tumour blood vessel calibre, and fractional tumour blood volume (fBV, %), in orthotopically propagated murine PC3 prostate tumour xenografts. Tumour vascular architecture was assessed in vivo by MRI prior to and 24 hr after treatment with 200 mg/kg of the vascular disrupting agent ZD6126. A Bayesian hierarchical model (BHM) was used to reduce the uncertainty associated with quantitation of R v and fBV. Quantitative histological analyses of the uptake of Hoechst 33342 for perfused vasculature, and haematoxylin and eosin staining for necrosis, were also performed to qualify the MRI data. A relatively large median R v of 40.3 μm (90% confidence interval (CI 90 ) = 37.4, 44.0 μm) and a high fBV of 5.4% (CI 90 = 5.3, 5.5%) were determined in control tumours, which agreed with histologically determined vessel size index. Treatment with ZD6126 significantly ( p < 0.01) reduced tumour R v (34.2μm, CI 90 = 31.2, 38.0 μm) and fBV (3.9%, CI 90 = 3.8, 4.1%), which were validated against histologically determined significant reductions in perfusion and vessel size, and increased necrosis. Together these data ( i ) highlight the use of a BHM to optimise the inferential power available from susceptibility contrast MRI data, ( ii ) provide strong evaluation and qualification of R v and fBV as non‐invasive imaging biomarkers of tumour vascular morphology, ( iii ) reveal the presence of a different vascular phenotype and ( iv ) demonstrate that ZD6126 exhibits good anti‐vascular activity against orthotopic prostate tumours.