Zachary H. Houston1,2*, Jens Bunt3, Linda J. Richards3, Kristofer J. Thurecht1,2


1Australian Institute for Bioengineering and Nanotechnology
and Centre for Advanced Imaging,
The University of Queensland, St Lucia, QLD, 4072, Australia.

2 ARC Centre of Excellence in Convergent BioNano Science and Technology
3 Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia


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). 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 model1,2, 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.