The Centre for Advanced Imaging 4^th Annual Symposium, 29^th of September, 2017.

Nanomaterials come in a plethora of designs, shapes, chemical formulations, sizes, and ionic forms and can be readily tuned to surpass many of the biological barriers within the body, but have had limited success in surpassing the final frontier of barriers: the blood-brain barrier (BBB).  While their size is a significant advantage of nanoparticles for their delivery to solid tumour masses, it is also their Achilles’ heel for crossing the BBB.  A major area of interest for nanoparticle therapeutics is the delivery to glioblastoma (GBM), as it is the most aggressive form of brain cancer.  Herein we report the use of simultaneous PET-MRI to develop a toolkit for monitoring tumour progression and its effect on BBB integrity of a spontaneous transgenic glioma model^1,2, for the purpose of establishing when the BBB is compromised enough for nanoparticles to cross.  A series of T1, T2, and dynamic contrast enhanced MRI images along with simultaneous PET of ¹⁸FDOPA were used to devise a set of in vivo imaging markers that could establish tumour volume and a measure of BBB integrity.  PET was again used to analyse the ability of a ⁶⁴Cu labelled bispecific antibody targeted hyperbranched polymer (HBP) ³ cross the BBB at different stages of GBM progression.  As expected, larger tumour volumes and a higher degree of leaky vasculature correlate with increased BBB permeability by the HBP.  This measure can be applied in the future to different sized nanoparticles and other materials to enable better development of BBB-penetrating nanocarriers.

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