Two-Part Study to Evaluate the Safety and Efficacy of Image Guided Surgery Using Indocyanine Green for Intramolecular Imaging of Nervous System Tumors Compared to Standard of Care, (TumorGlow)

Overview

Primary malignant and non-malignant brain tumors account for an estimated 21.42 cases per 100,000 for a total count of 343,175 incident tumors based on worldwide population estimates \[1\]. These entities result in variable but disappointing rates of survival, particularly for primary brain tumors (5-year survival rates: anaplastic astrocytoma 27%; glioblastoma multiforme 5%) \[2, 3\]. Metastatic brain tumors outnumber primary brain tumors (estimates as high as 10:1) as they affect approximately 25% of patients diagnosed with cancer \[4-6\]. In terms of brain tumor surgery, the extent of surgical resection-a factor that is greatly impacted by a Neurosurgeon's ability to visualize these tumors-is directly associated with patient outcomes and survival \[7-9\]. Although spinal cord tumors are lower in terms of their incidence \[10\], data correlating extent-of-resection to outcomes and survival have been demonstrated in patients with intramedullary tumors \[11\]. Using systemically delivered compounds with a high sensitivity of detection by near-infrared (NIR) fluorescence, it would be possible for us to improve surgical resection thus minimizing chances of recurrence and improving survival. Simply, if the tumor cells will "glow" during surgery, the surgeons are more likely to identify tumor margins and residual disease, and are, therefore more likely to perform a superior cancer operation. By ensuring a negative margin through NIR imagery, it would make it possible to decrease the rates of recurrence and thus improve overall survival. This concept of intraoperative molecular imaging requires two innovations: (i) a fluorescent contrast agent that can be injected systemically into the subject and that selectively accumulates in the tumor tissues, and (ii) an imaging system that can detect and quantify the contrast agent in the tumor tissues.\[12, 13\] Subjects undergo intraoperative imaging, receiving an injection of indocyanine green and then undergoing intraoperative imaging of the surgery site with a NIR imaging system. The imaging devices allow the operating field to be observed in real-time.

Indocyanine green is a water-soluble tricarbocyanine dye routinely used in clinical settings for measuring cardiac output, hepatic function, liver blood flow and ophthalmic angiography and has been in use for over 60 years \[14\]. This protocol utilizes Patheon's indocyanine green, NDC 17238-424. The chemical formula is C45H47N2O6S2Na and the compound has a molecular weight of 774.96Da (CAS number 3599-32-4). It has a peak absorption in the NIR spectrum at 800nm and maximal emission at 835nm. Indocyanine green is rapidly and completely bound to plasma proteins (especially albumin) after intravenous (IV) injection in the blood \[15\]. Indocyanine Green for Injection USP is a sterile, lyophilized green powder containing 25 mg of indocyanine green with no more than 5% sodium iodide. It is packaged with Sterile Water for Injection, USP, which is used to dissolve the indocyanine green, and is to be administered intravenously