A Computational Framework for the Administration of 5-Aminovulinic Acid before Glioblastoma Surgery

Abstract

5-Aminolevulinic Acid (5-ALA) is the only fluorophore approved by the FDA as an intraoperative optical imaging agent for fluorescence-guided surgery in patients with glioblastoma. The dosing regimen is based on rodent tests where a maximum signal occurs around 6 hours after drug administration. Here, we construct a computational framework to simulate the transport of 5-ALA through the stomach, blood, and brain, and the subsequent conversion to the florescent agent protoporphyrin IX at the tumor site. The framework combines compartmental models with spatially-resolved partial differential equations, enabling one to address questions regarding quantity and timing of 5-ALA administration before surgery. Numerical tests in two spatial dimensions indicate that, for tumors exceeding the detectable threshold, the time to peak flouresent concentration is 2-7 hours, broadly consistent with the current surgical guidelines. Moreover, the framework enables one to examine the specific effects of tumor size and location on the required dose and timing of 5-ALA administration before glioblastoma surgery.