Evaluation and Qualification of Non-Invasive MRI Biomarkers Associated with Platelet-Derived Growth Factor (PDGF) Signalling In Vivo. (360G-Wellcome-091763_Z_10_Z)

£188,220

This proposal is specifically concerned with investigating the use of both established (DCE-MRI) and emerging (susceptibility contrast, contrast enhanced T1-weighted MRI with slow infusion of Gd-DTPA) non-invasive MRI methods to interrogate the effects of PDGF expression and pericyte recruitment on vascular re-modelling, pharmacological vasoreactivity and therapeutic response in vivo. Given the dependence of solid tumour progression on angiogenesis, a murine B16 tumour model in which pericyte r ecruitment and maturation is increased through the expression of PDGF (B16/PDGF) will be utilised, and the data compared to that derived from control (B16/ctr) tumours. Initially, B16/ctr and B16/PDGF tumours will be characterised by DCE-MRI to establish the effect of increased pericyte coverage on vascular permeability. Subsequently, the ability of T1-weighted MRI with slow infusion of Gd-DTPA, a recently described approach to measure the spatial distribution and quantify tumour IFP, will be fully evaluated in this highly relevant and appropriate model system. Importantly, invasive wick-in-needle measurements will also be made to corroborate any differences in IFP. Subsequently, the response of B16/ctr and B16/PDGF tumours to a PDGF antagonist (CP-868596), an endothelin-1 antagonist (BQ123), and a vascular disrupting agent (ZD6126), all predicted to have a differential sensitivity against mature vasculature, will be investigated by MRI.

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Grant Details

Amount Awarded 188220
Applicant Surname Robinson
Approval Committee Physiological Sciences Funding Committee
Award Date 2010-07-06T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title Project Grant
Internal ID 091763/Z/10/Z
Lead Applicant Dr Simon Robinson
Partnership Value 188220
Planned Dates: End Date 2014-08-31T00:00:00+00:00
Planned Dates: Start Date 2010-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London