Radioluminescence Imaging of Drug Elution from Biomedical Implants

A method to noninvasively measure the concentration of radiolabeled pharmaceuticals on modified drug-eluting biomedical implant surfaces is described. The implants are coated with microphosphors and radiolabeled pharmaceuticals in a polyurethane film. The drug molecules emit radiation which excites radioluminescence in nearby phosphors; for drug released from the film the radiation is absorbed by the surrounding media and generates no light. The technique is applied to measure beta-emitting tritium-labeled vancomycin (H-3-vancomycin) concentration on the surface of an orthopedic plate. Bacteria can coat orthopedic implant surfaces and form biofilms which are resistant to antibiotics and the host's immune system. Antibiotic eluting implant coatings are thus promising candidates for infection prevention and treatment. Radioluminescence imaging permits surface-specific, noninvasive measurement of drug concentration on implant surfaces, which is an important metric for developing effective drug eluting coatings. The radioluminescence signal increases linearly with H-3-vancomycin concentration, with a limit of detection (LOD) of 9.6 nCi (3.5 pmol) without tissue. Biomedically relevant drug release concentrations are monitored through 5 mm of porcine tissue slices (38.7 nmol LOD). Despite light scattering, and an eightfold signal decrease through 5 mm of tissue, drug release and reference regions are resolvable for non-invasive quantification.