New Bifunctional Chelators Incorporating Dibromomaleimide Groups for Radiolabeling of Antibodies with Positron Emission Tomography Imaging Radioisotopes.
New Bifunctional Chelators Incorporating Dibromomaleimide Groups for Radiolabeling of Antibodies with Positron Emission Tomography Imaging Radioisotopes.
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DOI：
10.1021/acs.bioconjchem.0c00710
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发表时间：
2021-07-21
影响因子：
4.7
通讯作者：
Ma MT
中科院分区：
文献类型：
--
作者：
Farleigh M;Pham TT;Yu Z;Kim J;Sunassee K;Firth G;Forte N;Chudasama V;Baker JR;Long NJ;Rivas C;Ma MT
Positron Emission Tomography (PET) imaging with antibody-based contrast agents frequently uses the radioisotopes [64Cu]Cu2+ and [89Zr]Zr4+. The macrobicyclic chelator commonly known as sarcophagine (sar) is ideal for labeling receptor-targeted biomolecules with [64Cu]Cu2+. The siderophore chelator, desferrioxamine-B (dfo), has been widely used to incorporate [89Zr]Zr4+ into antibodies. Here, we describe new bifunctional chelators of sar and dfo: these chelators have been functionalized with dibromomaleimides (dbm), that enable site-specific and highly stable attachment of molecular cargoes to reduced, solvent-accessible, interstrand native disulfide groups. The new sar–dbm and dfo–dbm derivatives can be easily conjugated with the IgG antibody trastuzumab via reaction with reduced interstrand disulfide groups to give site-specifically modified dithiomaleamic acid (dtm) conjugates, sar–dtm–trastuzumab and dfo–dtm–trastuzumab, in which interstrand disulfides are rebridged covalently with a small molecule linker. Both sar– and dfo–dtm–trastuzumab conjugates have been radiolabeled with [64Cu]Cu2+ and [89Zr]Zr4+, respectively, in near quantitative radiochemical yield (>99%). Serum stability studies, in vivo PET imaging, and biodistribution analyses using these radiolabeled immunoconjugates demonstrate that both [64Cu]Cu-sar–dtm–trastuzumab and [89Zr]Zr-dfo–dtm–trastuzumab possess high stability in biological milieu. Dibromomaleimide technology can be easily applied to enable stable, site-specific attachment of radiolabeled chelators, such as sar and dfo, to native interstrand disulfide regions of antibodies, enabling tracking of antibodies with PET imaging.
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DOI：
10.1039/c3cc45220d
发表时间：
2013-09-25
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Castañeda L;Maruani A;Schumacher FF;Miranda E;Chudasama V;Chester KA;Baker JR;Smith ME;Caddick S
通讯作者：
Caddick S
影响因子：
4.7
作者：
Imberti C;Terry SY;Cullinane C;Clarke F;Cornish GH;Ramakrishnan NK;Roselt P;Cope AP;Hicks RJ;Blower PJ;Ma MT
通讯作者：
Ma MT
影响因子：
4.7
作者：
Bahou, Calise;Love, Elizabeth A.;Chudasama, Vijay
通讯作者：
Chudasama, Vijay
DOI：
10.1039/c4dt02978j
发表时间：
2015-03-21
期刊：
Dalton transactions (Cambridge, England : 2003)
影响因子：
--
作者：
Ma MT;Meszaros LK;Paterson BM;Berry DJ;Cooper MS;Ma Y;Hider RC;Blower PJ
通讯作者：
Blower PJ
影响因子：
4.7
作者：
Boswell, C. Andrew;Mundo, Eduardo E.;Lin, Kedan
通讯作者：
Lin, Kedan