文摘
The objective of this study was to characterize the in vitro and in vivo properties of the F(ab鈥?2 fragment of TRC105, a human/murine chimeric IgG1 monoclonal antibody that binds with high avidity to human and murine CD105 (i.e., endoglin), and investigate its potential for positron emission tomography (PET) imaging of tumor angiogenesis after 61/64Cu-labeling. TRC105-F(ab鈥?2 of high purity was produced by pepsin digestion of TRC105, which was confirmed by SDS鈥揚AGE, HPLC analysis, and mass spectrometry. 61/64Cu-labeling of NOTA-TRC105-F(ab鈥?2 (NOTA denotes 1,4,7-triazacyclononane-1,4,7-triacetic acid) was achieved with yields of >75% (specific activity: 115 GBq/渭mol). PET imaging revealed rapid tumor uptake of 64Cu-NOTA-TRC105-F(ab鈥?2 in the 4T1 murine breast cancer model (5.8 卤 0.8, 7.6 卤 0.6, 5.6 卤 0.4, 5.0 卤 0.6, and 3.8 卤 0.7% ID/g at 0.5, 3, 16, 24, and 48 h postinjection respectively; n = 4). Since tumor uptake peaked at 3 h postinjection, 61Cu-NOTA-TRC105-F(ab鈥?2 also gave good tumor contrast at 3 and 8 h postinjection. CD105 specificity of the tracers was confirmed by blocking studies and histopathology. In conclusion, the use of a F(ab鈥?2 fragment led to more rapid tumor uptake (which peaked at 3 h postinjection) than radiolabeled intact antibody (which often peaked after 24 h postinjection), which may allow for same day immunoPET imaging in future clinical studies.
Keywords:
positron emission tomography (PET); tumor angiogenesis; antibody fragment; F(ab鈥?2; CD105 (endoglin); breast cancer; 61Cu; 64Cu