{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:58:58Z","timestamp":1791244738439,"version":"4.1.0"},"reference-count":75,"publisher":"Radiation Research Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2024,12,31]]},"abstract":"<jats:p>BBT-059 is a long-acting PEGylated interleukin-11 analog that has been shown to have hematopoiesis-promoting and anti-apoptotic attributes, and is being studied as a radiation countermeasure for the hematopoietic acute radiation syndrome (H-ARS). This potential countermeasure has been demonstrated to enhance survival in irradiated mice. To investigate the toxicity and safety profile of this agent, 14 nonhuman primates (NHPs, rhesus macaques) were administered two different doses of BBT-059 subcutaneously 24 h after 4 Gy total-body irradiation and were monitored for the next 60 days postirradiation. Blood samples were investigated for the pharmacokinetics and pharmacodynamics of this agent and its effects on complete blood counts, cytokines, vital signs, and metabolomics. No adverse health effects were observed in either treatment group. Radiation-induced metabolomic dysregulation was observed in both treatment groups, and BBT-059 afforded some short-term radiomitigation. A few pathways were commonly dysregulated by radiation exposure including steroid hormone biosynthesis pathways, fatty acid activation, and glycerophospholipid metabolism. Notably, radiation-induced dysregulation to the linoleate metabolism pathway was significantly mitigated by either dose of BBT-059. In brief, this study suggests that BBT-059 has a good safety profile in irradiated NHPs and that its development as a medical countermeasure for U.S. Food and Drug Administration approval for human use should be continued.<\/jats:p>","DOI":"10.1667\/rade-24-00219.1","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T19:01:23Z","timestamp":1735585283000},"page":"83-95","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetic and Metabolomic Studies with BBT-059 in Nonhuman Primates Exposed to Total-Body Gamma Radiation"],"prefix":"10.1667","volume":"203","author":[{"given":"Alana D.","family":"Carpenter","sequence":"first","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, D.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issa Melendez","family":"Miranda","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Y.","family":"Wise","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluseyi O.","family":"Fatanmi","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Petrus","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Fam","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Boulder, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Boulder, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George N.","family":"Cox","sequence":"additional","affiliation":[{"name":"Bolder BioTechnology, Boulder, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita K.","family":"Cheema","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, D.C."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"60","doi-asserted-by":"crossref","unstructured":"CA Smith, EJ Want, G O'Maille, et al.  \"Anal Chem.\"  78, \"XCMS: Processing mass spectrometry data for metabolite profiling using Nonlinear peak alignment, matching, and identification.\" 779 (2006)","DOI":"10.1021\/ac051437y"},{"key":"75","unstructured":"\"Guide for the care and use of laboratory animals.\"  (2011)"},{"key":"67","doi-asserted-by":"crossref","unstructured":"SS Menon, M Uppal, S Randhawa, et al.  \"Front Oncol.\"  6, \"Radiation metabolomics: current status and future directions.\" 20 (2016)","DOI":"10.3389\/fonc.2016.00020"},{"key":"10","doi-asserted-by":"crossref","unstructured":"NP Clayton, RC Khan-Malek, CA Dangler, et al.  \"Radiat Res.\"  195, \"Sargramostim (rhu GM-CSF) improves survival of non-human primates with severe bone marrow suppression after acute, high-dose, whole-body irradiation.\" 191 (2021)","DOI":"10.1667\/RADE-20-00131.1"},{"key":"45","doi-asserted-by":"crossref","unstructured":"Y Li, M Girgis, SY Wise, et al.  \"Sci Rep.\"  11, \"Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure.\" 11449 (2021)","DOI":"10.1038\/s41598-021-91067-9"},{"key":"39","doi-asserted-by":"crossref","unstructured":"A Crook, A De Lima Leite, T Payne, et al.  \"Sci Rep.\"  11, \"Radiation exposure induces cross-species temporal metabolic changes that are mitigated in mice by amifostine.\" 14004 (2021)","DOI":"10.1038\/s41598-021-93401-7"},{"key":"1","doi-asserted-by":"crossref","unstructured":"JS. 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