BACKGROUND: Fluorescence-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. OBJECTIVE: To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma. METHODS: Patients 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. RESULTS: A 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. CONCLUSION: These results support the safety of tozuleristide at doses up to 30 mg and suggest that tozuleristide imaging may be useful for FGS of gliomas.
BACKGROUND: Fluorescence-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. OBJECTIVE: To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma. METHODS:Patients 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. RESULTS: A 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. CONCLUSION: These results support the safety of tozuleristide at doses up to 30 mg and suggest that tozuleristide imaging may be useful for FGS of gliomas.
Authors: Dongrui Wang; Renate Starr; Wen-Chung Chang; Brenda Aguilar; Darya Alizadeh; Sarah L Wright; Xin Yang; Alfonso Brito; Aniee Sarkissian; Julie R Ostberg; Li Li; Yanhong Shi; Margarita Gutova; Karen Aboody; Behnam Badie; Stephen J Forman; Michael E Barish; Christine E Brown Journal: Sci Transl Med Date: 2020-03-04 Impact factor: 17.956
Authors: Syed Muhammad Usama; Ek Raj Thapaliya; Michael P Luciano; Martin J Schnermann Journal: Curr Opin Chem Biol Date: 2021-03-05 Impact factor: 8.972
Authors: Alexander J Schupper; Manasa Rao; Nicki Mohammadi; Rebecca Baron; John Y K Lee; Francesco Acerbi; Constantinos G Hadjipanayis Journal: Front Neurol Date: 2021-06-16 Impact factor: 4.003
Authors: Servando Hernandez Vargas; Christie Lin; Hop S Tran Cao; Naruhiko Ikoma; Solmaz AghaAmiri; Sukhen C Ghosh; Adam J Uselmann; Ali Azhdarinia Journal: Front Oncol Date: 2021-06-30 Impact factor: 6.244