Radiolabeling and preliminary biodistribution study of 99mTc-labeled antibody-mimetic scaffold protein repebody for initial clearance properties

[Display omitted] Antibody-mimetic proteins are intensively being developed for biomedical applications including tumor imaging and therapy. Among them, repebody is a new class of protein that consists of highly diverse leucine-rich repeat (LRR) modules. Although all possible biomedical applications...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2017-11, Vol.27 (22), p.5060-5064
Hauptverfasser: Mushtaq, Sajid, Rho, Jong Kook, Kang, Jung Ae, Lee, Joong-Jae, Kim, Jung Young, Nam, You Ree, Yun, Seong-Jae, Lee, Gyeong Hee, Park, Sang Hyun, Lee, Dong-Eun, Kim, Hak-Sung
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Sprache:eng
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Zusammenfassung:[Display omitted] Antibody-mimetic proteins are intensively being developed for biomedical applications including tumor imaging and therapy. Among them, repebody is a new class of protein that consists of highly diverse leucine-rich repeat (LRR) modules. Although all possible biomedical applications with repebody are ongoing, it’s in vivo biodistribution and excretion pathway has not yet been explored. In this study, hexahistidine (His6)-tag bearing repebody (rEgH9) was labeled with [99mTc]-tricarbonyl, and biodistribution was performed following intravenous (I.V.) or intraperitoneal (I.P.) injection. Repebody protein was radiolabeled with high radiolabeling efficiency (>90%) and radiolabeled compound was more than 99% pure after purification. Biodistribution data indicates radiotracer has a rapid clearance from blood and excreted through the kidneys for intravenous (I.V.) injection, but comparatively slow clearance for an intraperitoneal (I.P.) injection. SPECT-CT images were found to be in agreement with biodistribution data, high activity was found inside kidneys. The observed result for rapid blood clearance and renal excretion of repebody (rEgH9) provide useful information for the further development of therapeutic strategy.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2017.09.047