Biomedical
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
Key Questions
What is the primary objective of this study?
The study aims to develop a trimodal imaging system that integrates Positron Emission Tomography (PET), Focused Ultrasound (FUS), and Magnetic Resonance Imaging (MRI) to facilitate real-time measurement of radiolabeled therapeutic agents' influx, particularly in glioblastoma treatment.
Why is there a need for integrating PET, FUS, and MRI modalities?
Integrating these modalities allows researchers to optimize the timing and dosage of therapeutic agents relative to FUS application, enhancing the delivery of treatments across the blood-brain and blood-tumor barriers, which are significant obstacles in treating brain tumors like glioblastoma.
What challenges does this study address in current glioblastoma treatments?
The study addresses the difficulty in determining the optimal timing and dosage of therapeutic agents when using FUS to disrupt the blood-brain and blood-tumor barriers, aiming to improve the efficacy of treatments by providing real-time imaging data.
What are the potential implications of this research?
This research could revolutionize the approach to delivering large molecule therapeutics and cell-based treatments for brain tumors by providing a method to monitor and optimize treatment delivery in real-time, potentially improving patient outcomes.
