Intracarotid RMP-7 enhanced indocyanine green staining of tumors in a rat glioma model

Objective: The extent of resection in patients with primary brain tumors may affect the quality of life, time to tumor progression, and survival. Currently, the extent of resection during surgery is guided by the visual appearance and consistency of tumor, frozen sections of the margins, intraoperative ultrasound, and frameless navigational systems and intraoperative imaging modalities. A new method that enhances the visualization of an infiltrating tumor and its margins may further aid in obtaining a more complete resection. A study was thus undertaken to assess the staining of brain tumors using Indocyanine green (ICG), a water-soluble emerald green tricarbocynanine dye concomitantly with RMP-7, a bradykinin analog, that selectively increases vascular permeability in brain tumors. Methods: A syngeneic ethyl-nitrosourea-induced F-344 rat cell line (36B-10) was stereotactically implanted into 25 rats, and allowed to mature for 15-18 days. Intracarotid administration of 0.75 ml of RMP-7 at a standard dose of 0.4 mug/ml over 15 min was then infused. Varying doses of ICG (range, 0-60 mg/kg) were then injected 15 min after the RMP-7 infusion ended. The animals were sacrificed 15 min after the ICG infusion was completed, and the brains examined macroscopically and microscopically for evidence of tumor staining. Results: This study demonstrated consistent staining of the tumor at only slightly lower ICG doses than previously described, however uptake at the tumor margins was evident at much lower doses. Thus the combination of ICG and RMP-7 administered preoperatively may provide visual enhancement of an infiltrating tumor and its margins to help facilitate a radical tumor removal.