10.1021/bc500415x.s001
Rubel Chakravarty
Rubel
Chakravarty
Shreya Goel
Shreya
Goel
Hector F. Valdovinos
Hector F.
Valdovinos
Reinier Hernandez
Reinier
Hernandez
Hao Hong
Hao
Hong
Robert J. Nickles
Robert J.
Nickles
Weibo Cai
Weibo
Cai
Matching the Decay Half-Life with the Biological Half-Life:
ImmunoPET Imaging with <sup>44</sup>Sc-Labeled Cetuximab Fab Fragment
American Chemical Society
2015
Fab
uptake
EGFR expression
PET imaging
epidermal growth factor receptor
positron emission tomography
tumor
87MG
44 Sc
4 h postinjection
day PET imaging
vivo PET imaging
ID
Cetuximab
2015-12-17 06:25:45
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Matching_the_Decay_Half_Life_with_the_Biological_Half_Life_ImmunoPET_Imaging_with_sup_44_sup_Sc_Labeled_Cetuximab_Fab_Fragment/2045652
Scandium-44
(<i>t</i><sub>1/2</sub> = 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 <sup>44</sup>Sc
for <i>in vivo</i> 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 <i>N</i>-[(R<i>)</i>-2-amino-3-(<i>para</i>-isothiocyanato-phenyl)propyl]-<i>trans</i>-(<i>S</i>,<i>S</i>)-cyclohexane-1,2-diamine-<i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>″,<i>N</i>″-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 <sup>44</sup>Sc labeling. PET imaging revealed
rapid tumor uptake (maximum uptake of ∼12% ID/g at 4 h postinjection)
of <sup>44</sup>Sc–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 <sup>44</sup>Sc–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.