Phase 1 Safety, Pharmacokinetics, and Fluorescence Imaging Study of Tozuleristide (BLZ-100) in Adults With Newly Diagnosed or Recurrent Gliomas.
Adult
Aged
Brain Neoplasms
/ diagnostic imaging
Dose-Response Relationship, Drug
Female
Fluorescent Dyes
/ administration & dosage
Glioma
/ diagnostic imaging
Humans
Indocyanine Green
/ administration & dosage
Injections, Intravenous
Male
Middle Aged
Neoplasm Recurrence, Local
/ diagnostic imaging
Optical Imaging
/ methods
Scorpion Venoms
/ administration & dosage
Brain neoplasms
Craniotomy
Cystine-knot miniproteins
Fluorescent dyes
Glioma
Journal
Neurosurgery
ISSN: 1524-4040
Titre abrégé: Neurosurgery
Pays: United States
ID NLM: 7802914
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
07
06
2018
accepted:
20
12
2018
pubmed:
10
5
2019
medline:
9
4
2020
entrez:
10
5
2019
Statut:
ppublish
Résumé
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. To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31069381
pii: 5486603
doi: 10.1093/neuros/nyz125
doi:
Substances chimiques
Fluorescent Dyes
0
Scorpion Venoms
0
tozuleristide
835UH424TU
Indocyanine Green
IX6J1063HV
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
E641-E649Informations de copyright
Copyright © 2019 by the Congress of Neurological Surgeons.