In Vitro Binding Kinetics of ChemoFilter with Cisplatin
- Author(s): Fisher, Joshua;
- Advisor(s): Hetts, Steven;
- et al.
Introduction: Endovascular chemotherapy treatment allows localized delivery adjacent to the target tumor; allowing an increased dosage and decreased leakage to other areas. It also allows for the opportunity to filter chemotherapy escaping the target tumor and entering the bloodstream. The ChemoFilter - a temporarily deployable, endovascular device will do just that; reducing systemic toxicity thus reducing adverse side effects from chemotherapy treatment. This will allow further increased dosage, increased tumor suppression, and increased tolerance to treatment. ChemoFilter has successfully filtered the chemotherapeutic Doxorubicin, but had yet to be tested in other chemotherapeutics. This study evaluates binding with new chemotherapeutics: Cisplatin, Carboplatin, and a cocktail comprised of Cisplatin and Doxorubicin.
Materials and Methods: ChemoFilter prototypes based on: 1.) Genomic DNA and
2.) Dowex (ion-exchange) resin, were evaluated for their ability to bind chemotherapy in vitro in phosphate-buffered saline (PBS). ChemoFilter was tested free in solution and encapsulated in nylon or polyester mesh packets of various dimensions. Concentrations were quantified using inductively coupled plasma mass spectrometry (IPC-MS), ultraviolet-visible spectrophotometry (UV-Vis), or fluorospectrometry. 11C, 13C, and/or 14C radiolabeling Carboplatin began for in vitro and in vivo ChemoFilter quantification. In vitro quantification can include scintillation and/or gamma counting. In vivo may include Positron Emission Tomography (PET) imaging, Hyperpolarized 13C Magnetic Resonance Imaging (MRI), and/or Magnetic Resonance Spectroscopy (MRS) for real-time visualization. Reactions were verified using High Performance Liquid Chromatography (HPLC) for chemical species identification.
Results and Discussion: Results indicate significant and nearly complete, ~99% (p<0.01) clearance of Cisplatin using the DNA ChemoFilter sequestered in Nylon mesh, quantified with gold standard ICP-MS (evidenced at 214 and 265 nm). The Ion-exchange ChemoFilter has significant clearance, within seconds, of both Doxorubicin and Cisplatin mixed in a cocktail solution. However, it appears some Cisplatin is binding to the Nylon Mesh itself. Size, shape, and material of the mesh have been optimized. A potential mechanism for 11C, 13C, or 14C radiolabeling of Carboplatin has been developed and early results have been successful. ChemoFilter works much more efficiently when sequestered in nylon packets of specific geometries. Significant improvements have been made to ChemoFilter, moving the device closer to clinical trials.