By a News Reporter-Staff News Editor at Life Science Weekly -- New research on Molecular Imaging is the subject of a report. According to news originating from Uppsala, Sweden, by NewsRx correspondents, research stated, "Affibody molecules, small scaffold proteins, have demonstrated an appreciable potential as imaging probes. Affibody molecules are composed of three alpha-helices."
Our news journalists obtained a quote from the research from Uppsala University, "Helices 1 and 2 are involved in molecular recognition, while helix 3 provides stability. The size of Affibody molecules can be reduced by omitting the third alpha-helix and cross-linking the two remaining, providing a smaller molecule with better extravasation and quicker clearance of unbound tracer. The goal of this study was to develop a novel 2-helix Affibody molecule based on backbone cyclization by native chemical ligation (NCL). The HER2-targeting NCL-cyclized Affibody molecule ZHER2:342min has been designed, synthesized and site-specifically conjugated with a DOTA chelator. DOTA-ZHER2:342min was labeled with (111)In and (68)Ga. The binding affinity of DOTA-ZHER2:342min was evaluated in vitro. The targeting properties of (111)In-and (68)Ga-DOTA-ZHER2:342min were evaluated in mice bearing SKOV-3 xenografts and compared with the properties of (111)In-and (68)Ga-labeled PEP09239, a DOTA-conjugated 2-helix Affibody analogue cyclized by a homocysteine disulfide bridge. The dissociation constant (KD) for DOTA-ZHER2:342min binding to HER2 was 18nM according to SPR measurements. DOTA-ZHER2:342min was labeled with (111)In and (68)Ga. Both conjugates demonstrated bi-phasic binding kinetics to HER2-expressing cells, with KD1 in low nanomolar range. Both variants demonstrated specific uptake in HER2-expressing xenografts. Tumor-to-blood ratios at 2h p.i. were 6.1±1.3 for (111)In-DOTA-ZHER2:342min and 4.6±0.7 for (68)Ga-DOTA-ZHER2:342min. However, the uptake of DOTA-ZHER2:342min in lung, liver and spleen was appreciably higher than the uptake of PEP09239-based counterparts."
According to the news editors, the research concluded: "Native chemical ligation enables production of a backbone-cyclized HER2-binding 2-helix Affibody molecule (ZHER2:342min) with low nanomolar target affinity and specific tumor uptake."
For more information on this research see: Evaluation of backbone-cyclized HER2-binding 2-helix affibody molecule for in vivo molecular imaging. Nuclear Medicine and Biology, 2013;40(3):378-86. (Elsevier - www.elsevier.com; Nuclear Medicine and Biology - www.elsevier.com/wps/product/cws_home/525482)
The news correspondents report that additional information may be obtained from H. Honarvar, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 81 Uppsala, Sweden. Additional authors for this research include N. Jokilaakso, K. Andersson, J. Malmberg, D. Rosik, A. Orlova, A.E. Karlstrom, V. Tolmachev and P. Jarver (see also Molecular Imaging).
Keywords for this news article include: Sweden, Europe, Uppsala, Nanotechnology, Molecular Imaging, Emerging Technologies.
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