Fabrication and Testing of a PET insert for Simultaneous PET/FUS/MRI

Abstract

Glioblastoma (GB) is the most common brain cancer and has limited survivability with a mean survival time of 15 months and an overall survival of less than 7 % after 5 years. Impediments to delivery of large molecule (e.g. antibodies) and cell therapeutics to a tumor include the blood–brain barrier (BBB) and the blood‐tumor barrier (BTB) which prevent large solutes from crossing from circulating blood into the extracellular fluid of the central nervous system. Recently, methodology has been developed to use focused ultrasound (FUS) in conjunction with microbubbles to temporarily disrupt the BBB/BTB. FUS units have been developed that can be used in the high magnetic fields that are part of a MRI scanners. The MRI is used to locate the brain tumor to determine where FUS energy will be applied to open the BBB/BTB. However, it is difficult using current technologies to determine the optimum relative timing and dosages of drugs/cells and application of FUS. We have previously shown using PET imaging of a [89Zr]‐mCD47 to GB in a mouse model, that antibody binding by a tumor is significantly enhanced if the mCD47 antibody is injected 15 min after BBB/BTB disruption, rather than injection before BBB/BTB disruption.1 However, this study was done using two fixed time points. The animals had to be transported between different scanners which prevented us from a continuous measurement of tumor uptake and washout of antibody. We propose to build a unique trimodal MRI/FUS/PET system that would permit real‐time measurement of influx of radiolabeled therapeutic antibodies or cells and allow us to optimize the timing of FUS relative to injection of therapeutics. It will allow whole‐body mouse imaging so we will be able to measure in vivo biodistribution as well. To the best of our knowledge, no such system exists anywhere. However, our group has previously published simulation studies that show that it is feasible to use a PET insert in conjunction with MRI and FUS in the setting of tumor ablation in the brain