Open AccessClick-Chemistry Strategy for Labeling Antibodies with Copper-64 via a Cross-Bridged Tetraazamacrocyclic Chelator Scaffold
Author(s) -
Amit Kumar,
Guiyang Hao,
Li Liu,
Saleh Ramezani,
Jer Tsong Hsieh,
Orhan K. Öz,
Xiankai Sun
Publication year - 2015
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.5b00102
Subject(s) - chemistry , click chemistry , tetrazine , antibody , in vivo , combinatorial chemistry , biophysics , organic chemistry , immunology , biology , microbiology and biotechnology
We report a click-chemistry based modular strategy for antibody labeling with (64)Cu (t1/2 = 12.7 h; β(+) 0.656 MeV, 17.4%; β(-) 0.573 MeV, 39%; EC 43%) under ambient condition utilizing a cross-bridged tetraazamacrocyclic (CB-TE2A) analogue, which otherwise requires harsh conditions that make the CB-TE2A analogues under-utilized for protein labeling despite the fact that they form kinetically inert copper complexes with high in vivo stability. Our strategy involves prelabeling a CB-TE2A based scaffold (CB-TE2A-1C) with (64)Cu and its subsequent reaction with an antibody via the tetrazine-norbornene mediated click chemistry. The effectiveness of this strategy was demonstrated by labeling two monoclonal antibodies, an anti-PSMA antibody (YPSMA-1) and a chimeric anti-phosphatidylserine antibody (Bavituximab). The immunoreactivity of the antibodies remained unchanged after the tetrazine modification and click-chemistry (64)Cu labeling. To further demonstrate the practicality of the modular (64)Cu labeling strategy, we tested positron emission tomography (PET) imaging of tumor with the (64)Cu-labeled bavituximab in a mouse xenograft model. The tumor visualization and uptake of the labeled antibody exhibited the versatility of the click-chemistry strategy.