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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\u00b7ng\/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are &gt;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.<\/jats:p>","DOI":"10.1177\/1091581817697685","type":"journal-article","created":{"date-parts":[[2017,3,17]],"date-time":"2017-03-17T04:20:14Z","timestamp":1489724414000},"page":"104-112","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":50,"title":["Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent"],"prefix":"10.1177","volume":"36","author":[{"given":"Julia","family":"Parrish-Novak","sequence":"first","affiliation":[{"name":"Blaze Bioscience, Inc, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Byrnes-Blake","sequence":"additional","affiliation":[{"name":"Northwest PK Solutions, LLC, Sultan, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narine","family":"Lalayeva","sequence":"additional","affiliation":[{"name":"SNBL USA, Ltd, Everett, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Burleson","sequence":"additional","affiliation":[{"name":"Burleson Research Technologies, Inc, Morrisville, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janean","family":"Fidel","sequence":"additional","affiliation":[{"name":"Veterinary Teaching Hospital, Washington State University, Pullman, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda","family":"Gilmore","sequence":"additional","affiliation":[{"name":"Xenometrics LLC, Stilwell, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Gayheart-Walsten","sequence":"additional","affiliation":[{"name":"Xenometrics LLC, Stilwell, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Bricker","sequence":"additional","affiliation":[{"name":"Xenometrics LLC, Stilwell, KS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"William J.","family":"Crumb","sequence":"additional","affiliation":[{"name":"CytoBiosciences, New Orleans, LA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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