• Chirag G Patil, David G Walker, Dennis M Miller, Pramod Butte, Beth Morrison, David S Kittle, Stacey J Hansen, Kaitlin L Nufer, Kelly A Byrnes-Blake, Miko Yamada, Lynlee L Lin, Kim Pham, Jeff Perry, Julia Parrish-Novak, Laura Ishak, Tarl Prow, Keith Black, and Adam N Mamelak.
• Cedars-Sinai Medical Center, Los Angeles, California.
• Neurosurgery. 2019 Oct 1; 85 (4): E641-E649.

BackgroundFluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate molecule for FGS of glioma and other tumor types.ObjectiveTo perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma.MethodsPatients received a single intravenous dose of tozuleristide 3 to 29 h before surgery. Fluorescence images of tumor and cavity in Situ before and after resection and of excised tissue ex Vivo were acquired, along with safety and pharmacokinetic measures.ResultsA total of 17 subjects received doses between 3 and 30 mg. No dose-limiting toxicity was observed, and no reported adverse events were considered related to tozuleristide. At doses of 9 mg and above, the terminal serum half-life for tozuleristide was approximately 30 min. Fluorescence signal was detected in both high- and low-grade glial tumors, with high-grade tumors generally showing greater fluorescence intensity compared to lower grade tumors. In high-grade tumors, signal intensity increased with increased dose levels of tozuleristide, regardless of the time of dosing relative to surgery.ConclusionThese results support the safety of tozuleristide at doses up to 30 mg and suggest that tozuleristide imaging may be useful for FGS of gliomas.Copyright © 2019 by the Congress of Neurological Surgeons.

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