Article ; Online: Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.
International journal of toxicology
2017 Volume 36, Issue 2, Page(s) 104–112
Abstract: BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. ... ...
| Abstract | BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials. |
|---|---|
| MeSH term(s) | Animals ; Complement System Proteins/analysis ; Dogs ; Drug Hypersensitivity/blood ; Female ; Fluorescent Dyes/pharmacokinetics ; Fluorescent Dyes/toxicity ; HEK293 Cells ; Histamine/blood ; Humans ; Indocyanine Green/analogs & derivatives ; Indocyanine Green/pharmacokinetics ; Indocyanine Green/toxicity ; Macaca fascicularis ; Male ; Mice ; Neoplasms/diagnostic imaging ; Neoplasms/metabolism ; Rats, Sprague-Dawley ; Scorpion Venoms/blood ; Scorpion Venoms/pharmacokinetics ; Scorpion Venoms/toxicity |
| Chemical Substances | Fluorescent Dyes ; Scorpion Venoms ; Histamine (820484N8I3) ; tozuleristide (835UH424TU) ; Complement System Proteins (9007-36-7) ; Indocyanine Green (IX6J1063HV) |
| Language | English |
| Publishing date | 2017-03-17 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 1379845-5 |
| ISSN | 1092-874X ; 1091-5818 |
| ISSN (online) | 1092-874X |
| ISSN | 1091-5818 |
| DOI | 10.1177/1091581817697685 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 1870: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.