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Matching the Decay Half-Life with the Biological Half-Life: ImmunoPET Imaging with 44Sc-Labeled Cetuximab Fab Fragment
journal contribution
posted on 2015-12-17, 06:25 authored by Rubel Chakravarty, Shreya Goel, Hector F. Valdovinos, Reinier Hernandez, Hao Hong, Robert J. Nickles, Weibo CaiScandium-44
(t1/2 = 3.9 h) is a relatively
new radioisotope of potential interest for use in clinical positron
emission tomography (PET). Herein, we report, for the first time,
the room-temperature radiolabeling of proteins with 44Sc
for in vivo PET imaging. For this purpose, the Fab
fragment of Cetuximab, a monoclonal antibody that binds with high
affinity to epidermal growth factor receptor (EGFR), was generated
and conjugated with N-[(R)-2-amino-3-(para-isothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N′,N″,N″-pentaacetic acid (CHX-A″-DTPA).
The high purity of Cetuximab-Fab was confirmed by SDS-PAGE and mass
spectrometry. The potential of the bioconjugate for PET imaging of
EGFR expression in human glioblastoma (U87MG) tumor-bearing mice was
investigated after 44Sc labeling. PET imaging revealed
rapid tumor uptake (maximum uptake of ∼12% ID/g at 4 h postinjection)
of 44Sc–CHX-A″-DTPA–Cetuximab-Fab
with excellent tumor-to-background ratio, which might allow for same
day PET imaging in future clinical studies. Immunofluorescence staining
was conducted to correlate tracer uptake in the tumor and normal tissues
with EGFR expression. This successful strategy for immunoPET imaging
of EGFR expression using 44Sc–CHX-A″-DTPA–Cetuximab-Fab
can make clinically translatable advances to select the right population
of patients for EGFR-targeted therapy and also to monitor the therapeutic
efficacy of anti-EGFR treatments.