TY - JOUR
AU - Cornelissen, Bart
AB - 111 89 Purpose The efficacy of most anticancer treatments, includ- vious results using In-anti-γH2AX-TAT. Retention of Zr- ing radiotherapy, depends on an ability to cause DNA double- anti-γH2AX-TAT was eightfold higher at 1 h post irradiation, strand breaks (DSBs). Very early during the DNA damage in cells expressing γH2AX, compared to non-irradiated cells signalling process, the histone isoform H2AX is phosphory- or to non-specific IgG control. PET imaging of mice showed lated to form γH2AX. With the aim of positron emission higher uptake of Zr-anti-γH2AX-TAT in irradiated xeno- tomography (PET) imaging of DSBs, we synthesized a Zr- grafts, compared to non-irradiated or non-specific controls labelled anti-γH2AX antibody, modified with the cell- (12.1±1.6 vs 5.2±1.9 and 5.1±0.8 %ID/g, respectively; penetrating peptide, TAT, which includes a nuclear localiza- p<0.0001). The mean absorbed dose to the nucleus of cells tion sequence. taking up Zr-anti-γH2AX-TAT was twofold lower com- Methods Zr-anti-γH2AX-TAT was synthesized using EDC/ pared to In-anti-γH2AX-TAT. Additional exposure of nei- NHS chemistry for TAT peptide linkage. Desferrioxamine ther irradiated nor non-irradiated cells nor tissues to Zr- conjugation allowed labelling with Zr. Uptake and retention anti-γH2AX-TAT resulted in any significant changes in the of Zr-anti-γH2AX-TAT was evaluated in the breast adeno- number 
TI - PET imaging of DNA damage using 89Zr-labelled anti-γH2AX-TAT immunoconjugates
JF - European Journal of Nuclear Medicine and Molecular Imaging
DO - 10.1007/s00259-015-3092-8
DA - 2015-06-02
UR - https://www.deepdyve.com/lp/springer-journals/pet-imaging-of-dna-damage-using-89zr-labelled-anti-h2ax-tat-CZeGF9bQq3
SP - 1707
EP - 1717
VL - 42
IS - 11
DP - DeepDyve
ER -