Diagnostic Performance of Fluorescein as an Intraoperative Brain Tumor Biomarker

Consenting subjects who have met inclusion and exclusion criteria will be enrolled to receive either fluorescein+ALA or fluorescein alone. HGG patients will be randomized on a 2 to 1 basis to receive either both fluorescein and ALA or fluorescein alone, and LGG patients will be randomized on a 1 to 1 basis.

This study is a diagnostic trial of fluorescein fluorescence as an intraoperative imaging biomarker during open cranial surgery for tumor resection of first-time (preoperatively) presumed high or low grade glioma. Subjects participate in a "one-time" event/visit (i.e, surgery) as part of this protocol. Images and data from the patient's pre- and post-operative MR scans are used for analysis in the study, but these acquisitions are part of the patient's standard-of-care, would occur independently of whether the participant is enrolled; and thus, are not considered to be research study visits. No post-surgical follow-up visit is part of the protocol data collection or analysis. Patients are monitored for possible adverse events through the routine follow-up under the care of the operating surgeon involved in the study procedures, post-operatively and subsequently through the medical record. Hence, this information is already being collected as part of standard-of-care and is available for adverse event surveillance. Patients receiving ALA who present with abnormally elevated LFTs beyond the peri-operative observation period are monitored on a regular basis until resolution and this blood testing is considered to be part of the study.

Administration of study drug:

Patients enrolled in the fluorescein+ALA arm will be administered orally 5-ALA (DUSA Pharmaceuticals, Tarrytown, NY) at 20 mg/kg body weight, dissolved in 100 ml of water, approximately 3 hours prior to the induction of anesthesia.

For patients receiving only fluorescein, the operating surgeon will request bolus injection (at a dose of 5 mg/kg) approximately 30 minutes prior to the start of tumor resection. For especially long cases (e.g., > 4 h) or if fluorescein fluorescence dissipates substantially during the course of the procedure, a second bolus injection may occur later in the case.

Inclusion criteria

• Preoperative diagnosis of either presumed first-time low or high grade glioma (astrocytoma, oligodendroglioma, mixed oligo-astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme).
• Tumor judged to be suitable for open cranial resection based on preoperative imaging studies.
• Valid informed consent by subject or subject's LAR.
• No serious associated psychiatric illnesses.
• Age ≥ 21 years old.

Exclusion criteria

• Pregnant women or women who are breast feeding.
• History of hypersensitivity to fluorescein.
• History of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins, photodermatosis, exfoliative dermatitis.
• History of liver disease within the last 12 months.
• Elevated LFTs (AST, ALT, ALP or bilirubin levels greater than 2.5 times the normal limit) from laboratory tests conducted within 30 days prior to surgery.
• Serum creatinine in excess of 180µmol/L (2.04 md/dL) within 30 days prior to surgery.
• Inability to comply with the photosensitivity precautions associated with the study.