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:

1. Preoperative diagnosis of either presumed first-time low or high grade glioma
(astrocytoma, oligodendroglioma, mixed oligo-astrocytoma, anaplastic astrocytoma, and
glioblastoma multiforme).

2. Tumor judged to be suitable for open cranial resection based on preoperative imaging
studies.

3. Valid informed consent by subject or subject's LAR.

4. No serious associated psychiatric illnesses.

5. Age ≥ 21 years old.

Exclusion Criteria:

1. Pregnant women or women who are breast feeding.

2. History of hypersensitivity to fluorescein.

3. History of cutaneous photosensitivity, porphyria, hypersensitivity to porphyrins,
photodermatosis, exfoliative dermatitis.

4. History of liver disease within the last 12 months.

5. 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.

6. Serum creatinine in excess of 180µmol/L (2.04 md/dL) within 30 days prior to surgery.

7. Inability to comply with the photosensitivity precautions associated with the study.