• Optimum dose and administration time of aminolevulinic acid for the detection of residual tumor by fluorescence imaging [ Designated as safety issue: No ]
  

• Correlation between intensity of in vivo fluorescence and the pathologist's quantification of tumor in biopsy specimens (e.g., percentage of tumor present) as measured by PpIX concentration and intra-operative fluorescence intensity [ Designated as safety issue: No ]
  
• Correlation between the amount and location of residual tumor detected intraoperatively by fluorescence imaging and frameless stereotaxy after maximal resection and the post-operative image enhancement on CT scan and/or MRI [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To determine the optimum dose and administration time of aminolevulinic acid that yields the highest diagnostic accuracy for residual tumor detection by in vivo quantitative fluorescence imaging in patients with grade IV malignant astrocytoma undergoing surgical resection.

Secondary

• To correlate the in vivo quantitative fluorescence signal with the absolute PpIX concentration by confocal fluorescence microscopy in tissue samples from these patients.

Tertiary

• To determine the relationship between the presence of fluorescence in the surgical cavity, in terms of the amount and location of residual tumor detected intraoperatively by fluorescence imaging and frameless stereotaxy after maximal resection, and the post-operative image enhancement on CT scan and/or MRI.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical site and disease status (de novo vs recurrent). Patients are randomized to 1 of 9 treatment arms.

• Arm I: Patients receive low-dose oral aminolevulinic acid at 2 hours before the midpoint of surgery.
• Arm II: Patients receive low-dose oral aminolevulinic acid at 6 hours before the midpoint of surgery.
• Arm III: Patients receive low-dose oral aminolevulinic acid at 12 hours before the midpoint of surgery.
• Arm IV: Patients receive medium-dose oral aminolevulinic acid at 2 hours before the midpoint of surgery.
• Arm V: Patients receive medium-dose oral aminolevulinic acid at 6 hours before the midpoint of surgery.
• Arm VI: Patients receive medium-dose oral aminolevulinic acid at 12 hours before the midpoint of surgery.
• Arm VII: Patients receive high-dose oral aminolevulinic acid at 2 hours before the midpoint of surgery.
• Arm VIII: Patients receive high-dose oral aminolevulinic acid at 6 hours before the midpoint of surgery.
• Arm IX: Patients receive high-dose oral aminolevulinic acid at 12 hours before the midpoint of surgery.

Patients in all arms undergo quantitative fluorescence imaging of tumor tissue and normal tissue at approximately the midpoint of surgery and then after maximal resection of the tumor. Tumor tissue samples are obtained at the same two timepoints of fluorescence imaging and are analyzed for histopathology, PpIX quantification by spectrofluorimetry, and PpIX microdistribution by confocal fluorescence microscopy.