Evaluating Radioactive Analogs of Doxorubicin to Quantify ChemoFilter Binding and Whole-Body Positron Emission Tomography/Magnetic Resonance Imaging for Drug Biodistribution.

PURPOSE: To evaluate radiolabeled doxorubicin (Dox) analogs as tracers of baseline Dox biodistribution in vivo during hepatic intra-arterial chemotherapy and to assess the efficacy of ChemoFilter devices to bind Dox in vitro. MATERIALS AND METHODS: In an in vitro static experiment, [fluorine-18]N-succinimidyl 4-fluorobenzoate ([18F]SFB) and [fluorine-18]fluorobenzoyl-doxorubicin ([18F]FB-Dox) were added to a beaker containing a filter material (Dowex cation exchange resin, single-stranded DNA (ssDNA) resin, or sulfonated polymer coated mesh). In an in vitro flow model, [18F]FB-Dox was added into a Dox solution in phosphate-buffered saline, and the solution flowed via a syringe column containing the filter materials. In an in vitro flow experiment, using micro-positron emission tomography (PET), images were taken as [18F]SFB and [18F]FB-Dox moved through a phantom. For in vivo biodistribution testing, a catheter was placed into the common hepatic artery of a swine, and [18F]FB-Dox was infused over 30 seconds. A 10-minute dynamic image and three 20-minute static images were acquired using 3T PET/MR imaging. RESULTS: In the in vitro static experiment, [18F]FB-Dox demonstrated 76.7%, 88.0%, and 52.4% binding to the Dowex resin, ssDNA resin, and coated mesh, respectively. In the in vitro flow model, the first-pass binding of [18F]FB-Dox to the Dowex resin, ssDNA resin, and coated mesh was 76.7%, 74.2%, and 76.2%, respectively, and the total bound fraction was 80.9%, 84.6%, and 79.9%, respectively. In the in vitro flow experiment using micro-PET, the phantom demonstrated a greater amount of [18F]FB-Dox bound to both filter cartridges than of the control [18F]SFB. In in vivo biodistribution testing, the first 10 minutes depicted [18F]FB-Dox moving through the right upper quadrant of the abdomen. A region-of-interest analysis showed that the relative amount increased by 2.97 times in the gallbladder and 1.08 times in the kidney. The amount decreased by 0.74 times in the brain and 0.57 times in the heart. CONCLUSIONS: [18F]FB-Dox can be used to assess Dox binding to ChemoFilters as well as in vivo biodistribution. This sets the stage for the evaluation of ChemoFilter effectiveness in reducing systemic toxicity from intra-arterial chemotherapy.

Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention.

Background For patients with acute ischemic stroke undergoing endovascular mechanical thrombectomy with x-ray angiography, the use of adjuncts to maintain vessel patency, such as stents or antiplatelet medications, can increase risk of periprocedural complications. Criteria for using these adjuncts are not well defined. Purpose To evaluate use of MRI to guide critical decision making by using a combined biplane x-ray neuroangiography 3.0-T MRI suite during acute ischemic stroke intervention. Materials and Methods This retrospective observational study evaluated consecutive patients undergoing endovascular intervention for acute ischemic stroke between July 2019 and May 2020 who underwent either angiography with MRI or angiography alone. Cerebral tissue viability was assessed by using MRI as the reference standard. For statistical analysis, Fisher exact test and Student t test were used to compare groups. Results Of 47 patients undergoing acute stroke intervention, 12 patients (median age, 69 years; interquartile range, 60-77 years; nine men) underwent x-ray angiography with MRI whereas the remaining 35 patients (median age, 80 years; interquartile range, 68-86 years; 22 men) underwent angiography alone. MRI results influenced clinical decision making in one of three ways: whether or not to perform initial or additional mechanical thrombectomy, whether or not to place an intracranial stent, and administration of antithrombotic or blood pressure medications. In this initial experience, decision making during endovascular acute stroke intervention in the combined angiography-MRI suite was better informed at MRI, such that therapy was guided in real time by the viability of the at-risk cerebral tissue. Conclusion Integrating intraprocedural 3.0-T MRI into acute ischemic stroke treatment was feasible and guided decisions of whether or not to continue thrombectomy, to place stents, or to administer antithrombotic medication or provide blood pressure medications. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lev and Leslie-Mazwi in this issue.

MRI-guided endovascular intervention: current methods and future potential.

INTRODUCTION: Image-guided endovascular interventions, performed using the insertion and navigation of catheters through the vasculature, have been increasing in number over the years, as minimally invasive procedures continue to replace invasive surgical procedures. Such endovascular interventions are almost exclusively performed under x-ray fluoroscopy, which has the best spatial and temporal resolution of all clinical imaging modalities. Magnetic resonance imaging (MRI) offers unique advantages and could be an attractive alternative to conventional x-ray guidance, but also brings with it distinctive challenges. AREAS COVERED: In this review, the benefits and limitations of MRI-guided endovascular interventions are addressed, systems and devices for guiding such interventions are summarized, and clinical applications are discussed. EXPERT OPINION: MRI-guided endovascular interventions are still relatively new to the interventional radiology field, since significant technical hurdles remain to justify significant costs and demonstrate safety, design, and robustness. Clinical applications of MRI-guided interventions are promising but their full potential may not be realized until proper tools designed to function in the MRI environment are available. Translational research and further preclinical studies are needed before MRI-guided interventions will be practical in a clinical interventional setting.

A bioinspired elastin-based protein for a cytocompatible underwater adhesive.

The development of adhesives that can be applied and create strong bonds underwater is a significant challenge for materials engineering. When the adhesive is intended for biomedical applications, further criteria, such as biocompatibility, must be met. Current biomedical adhesive technologies do not meet these needs. In response, we designed a bioinspired protein system that shows promise to achieve biocompatible underwater adhesion coupled with environmentally responsive behavior that is "smart" - that is, it can be tuned to suit a specific application. The material, ELY16, is constructed from an elastin-like polypeptide (ELP) that can be produced in high yields from Escherichia coli and can coacervate in response to environmental factors such as temperature, pH, and salinity. To confer wet adhesion, we utilized design principles from marine organisms such as mussels and sandcastle worms. When expressed, ELY16 is rich in tyrosine. Upon modification with the tyrosinase enzyme to form mELY16, the tyrosine residues are converted to 3,4-dihydroxyphenylalanine (DOPA). Both ELY16 and mELY16 exhibit cytocompatibility and significant dry adhesion strength (>2 MPa). Modification with DOPA increases protein adsorption to glass and provides moderate adhesion strength (∼240 kPa) in a highly humid environment. Furthermore, this ELP exhibits a tunable phase transition behavior that can be formulated to coacervate in physiological conditions and provides a convenient mechanism for application underwater. Finally, mELY16 possesses significantly higher adhesion strength in dry, humid, and underwater environments compared with a commercially available fibrin sealant. To our knowledge, mELY16 provides the strongest bonds of any rationally designed protein when used completely underwater, and its high yields make it more viable for commercial application compared to natural adhesive proteins. In conclusion, this ELP shows great potential to be a new "smart" underwater adhesive.