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.

3D Printed Absorber for Capturing Chemotherapy Drugs before They Spread through the Body.

Despite efforts to develop increasingly targeted and personalized cancer therapeutics, dosing of drugs in cancer chemotherapy is limited by systemic toxic side effects. We have designed, built, and deployed porous absorbers for capturing chemotherapy drugs from the bloodstream after these drugs have had their effect on a tumor, but before they are released into the body where they can cause hazardous side effects. The support structure of the absorbers was built using 3D printing technology. This structure was coated with a nanostructured block copolymer with outer blocks that anchor the polymer chains to the 3D printed support structure and a middle block that has an affinity for the drug. The middle block is polystyrenesulfonate which binds to doxorubicin, a widely used and effective chemotherapy drug with significant toxic side effects. The absorbers are designed for deployment during chemotherapy using minimally invasive image-guided endovascular surgical procedures. We show that the introduction of the absorbers into the blood of swine models enables the capture of 64 ± 6% of the administered drug (doxorubicin) without any immediate adverse effects. Problems related to blood clots, vein wall dissection, and other biocompatibility issues were not observed. This development represents a significant step forward in minimizing toxic side effects of chemotherapy.

Endovascular Ion Exchange Chemofiltration Device Reduces Off-Target Doxorubicin Exposure in a Hepatic Intra-arterial Chemotherapy Model.

Purpose: To determine if endovascular chemofiltration with an ionic device (ChemoFilter [CF]) can be used to reduce systemic exposure and off-target biodistribution of doxorubicin (DOX) during hepatic intra-arterial chemotherapy (IAC) in a preclinical model. Materials and Methods: Hepatic IAC infusions were performed in six pigs with normal livers. Animals underwent two 10-minute intra-arterial infusions of DOX (200 mg) into the common hepatic artery. Both the treatment group and the control group received initial IAC at 0 minutes and a second dose at 200 minutes. Prior to the second dose, CF devices were deployed in and adjacent to the hepatic venous outflow tract of treatment animals. Systemic exposure to DOX was monitored via blood samples taken during IAC procedures. After euthanasia, organ tissue DOX concentrations were analyzed. Alterations in systemic DOX exposure and biodistribution were compared by using one-tailed t tests. Results: CF devices were well tolerated, and no hemodynamic, thrombotic, or immunologic complications were observed. Animals treated with a CF device had a significant reduction in systemic exposure when compared with systemic exposure in the control group (P <.009). Treatment with a CF device caused a significant decrease in peak DOX concentration (31%, P <.01) and increased the time to maximum concentration (P <.03). Tissue analysis was used to confirm significant reduction in DOX accumulation in the heart and kidneys (P <.001 and P <.022, respectively). Mean tissue concentrations in the heart, kidneys, and liver of animals treated with CF compared with those in control animals were 14.2 µg/g ± 1.9 (standard deviation) versus 26.0 µg/g ± 1.8, 46.4 µg/g ± 4.6 versus 172.6 µg/g ± 40.2, and 217.0 µg/g ± 5.1 versus 236.8 µg/g ± 9.0, respectively. Fluorescence imaging was used to confirm in vivo DOX binding to CF devices. Conclusion: Reduced systemic exposure and heart bioaccumulation of DOX during local-regional chemotherapy to the liver can be achieved through in situ adsorption by minimally invasive image-guided CF devices.© RSNA, 2019.

Accuracy of image-guided percutaneous injection into a phantom spinal cord utilizing flat panel detector CT with MR fusion and integrated navigational software.

PURPOSE: To evaluate the accuracy of percutaneous fluoroscopic injection into the spinal cord of a spine phantom utilizing integrated navigational guidance from fused flat panel detector CT (FDCT) and MR datasets. Conventional and convection-enhanced delivery (CED) techniques were evaluated. MATERIALS AND METHODS: FDCT and MR datasets of a swine thoracic spine phantom were co-registered using an integrated guidance system and surface to spinal cord target trajectory planning was performed on the fused images. Under real-time fluoroscopic guidance with pre-planned trajectory overlay, spinal cord targets were accessed via a coaxial technique. Final needle tip position was compared with a pre-determined target on 10 independent passes. In a subset of cases, contrast was injected into the central spinal cord with a 25G spinal needle or customized 200 µm inner diameter step design cannula for CED. RESULTS: Average needle tip deviation from target measured 0.92±0.5 mm in the transverse, 0.47±0.4 mm in the anterior-posterior, and 1.67±1.2 mm in the craniocaudal dimension for an absolute distance error of 2.12±1.12 mm. CED resulted in elliptical intramedullary diffusion of contrast compared with primary reflux observed with standard needle injection. CONCLUSIONS: These phantom feasibility data demonstrate a minimally invasive percutaneous approach for targeted injection into the spinal cord utilizing real-time fluoroscopy aided by overlay trajectories derived from fused MRI and FDCT data sets with a target error of 2.1 mm. Intramedullary diffusion of injectate in the spinal cord is facilitated with CED compared with standard injection technique. Pre-clinical studies in large animal models are warranted.

Dynamic Measurement of Arterial Liver Perfusion With an Interventional C-Arm System.

PURPOSE: Objective intraprocedural measurement of hepatic blood flow could provide a quantitative treatment end point for locoregional liver procedures. This study aims to validate the accuracy and reproducibility of cone-beam computed tomography perfusion (CBCTp) measurements of arterial liver perfusion (ALP) against clinically available computed tomography perfusion (CTp) measurements in a swine embolization model. METHODS: Triplicate CBCTp measurements using a selective arterial contrast injection were performed before and after complete embolization of the left lobe of the liver in 5 swine. Two CBCTp protocols were evaluated that differed in sweep duration (3.3 vs 4.5 seconds) and the number of acquired projection images (166 vs 248). The mean ALP was measured within identical volumes of interest selected in the embolized and nonembolized regions of the perfusion map generated from each scan. Postembolization CBCTp values were also compared with CTp measurements. RESULTS: The 2 CBCTp protocols demonstrated high concordance correlation (0.90, P < 0.001). Both CBCTp protocols showed higher reproducibility than CTp in the nontarget lobe, with an intraclass correlation of 0.90 or greater for CBCTp and 0.83 for CTp (P < 0.001 for all correlations). The ALP in the embolized lobe was nearly zero and hence excluded for reproducibility. High concordance correlation was observed between the CTp and each CBCTp protocol, with the shorter CBCTp protocol reaching a concordance correlation of 0.75 and the longer achieving 0.87 (P < 0.001 for both correlations). CONCLUSIONS: Dynamic blood flow measurement using an angiographic C-arm system is feasible and produces quantitative results comparable to CTp.