Abstract
1080
Objectives: Polypropylene mesh is commonly used for the repair of tissue in the gynecologic conditions that include pelvic organ prolapse and stress urinary incontinence, as well as for hernia repair. Unfortunately, polypropylene mesh has been associated with complications including mesh exposure through neighboring tissues, pain, and infection. In women who have had pelvic mesh-related complications and have had surgical removal of their mesh, it has been shown that the mesh-tissue-interface is characterized by an abundance of macrophages exhibiting a pro-inflammatory phenotype, and this characteristic response is seen years after initial mesh placement.1 The early kinetics of this characteristic macrophage response (e.g., recruitment and distribution) is currently unknown, due in part to a lack of non-invasive quantitative and longitudinal imaging strategies. PET imaging of the macrophage marker CD11b (αM) could be used to characterize the inflammation response around the meshes. The objective of this study is to visualize macrophage recruitment to the implant interface in a syngeneic murine model of subcutaneous polypropylene mesh implantation utilizing pre-clinical PET with a Zr-89-anti-CD11b monoclonal antibody (Mab, clone M1/70). Ultimately, quantification of macrophage infiltration dynamics at the implant interface could guide future treatment strategies aimed at the reprogramming and modulation of macrophage infiltration.2
Methods: Sheets of polypropylene mesh (Gynemesh® PS, Ethicon, Somerville, NJ) were cut into 1 x 1 cm pieces and washed in a 1:1 acetone:isopropanol solution, followed by a deionized H2O rinse, and then terminally sterilized with ethylene oxide gas. Eight to 10 week-old C57BL/6J female mice were anesthetized, the surgical abdominal area was prepped, and a right-of-midline excision created to subcutaneously implant the mesh. At eight days post-implantation, mice were injected (i.v.) with 89Zr-labeled CD11b Mab, and another cohort of mice were injected with 10-fold lower specific activity to block CD11b-mediated uptake. PET imaging was performed at 24, 48, 72, and 144 h post injection, and the mice were euthanized for tissue analysis.
Results: ROI analysis of the mesh regions demonstrated significant uptake of 89Zr-CD11b Mab around the meshes, which was reduced with a blocking dose. The best contrast was at 144 h. Biodistribution studies correlated with the PET data. Flow cytometry studies showed high levels of CD11b in the isolated meshes, which correlated with immunohistochemistry results. In conclusion, we have demonstrated PET imaging of CD11b+ macrophage recruitment to an implanted surgical mesh utilizing pre-clinical PET with a Zr-89-anti-CD11b Mab. ImmunoPET quantification of CD11b levels is a promising approach for inflammation imaging of surgical mesh implants.