Matching the decay half-life with the biological half-life: ImmunoPET imaging with (44)Sc-labeled cetuximab Fab fragment.
Scandium-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 (44)Sc 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 (44)Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of ∼12% ID/g at 4 h postinjection) of (44)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 (44)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.
Department of Radiology, University of Wisconsin-Madison , Madison, Wisconsin 53792, United States.
Rubel
R
Chakravarty
Shreya
S
Goel
Hector F
HF
Valdovinos
Reinier
R
Hernandez
Hao
H
Hong
Robert J
RJ
Nickles
Weibo
W
Cai
D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology; D018938:Caco-2 Cells; D000068818:Cetuximab / Q000737:chemistry*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005909:Glioblastoma / Q000175:diagnosis / Q000473:pathology; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D008819:Mice, Nude; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D012538:Scandium; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D007140:Immunoglobulin Fab Fragments; D011868:Radioisotopes; D004369:Pentetic Acid; D066246:ErbB Receptors; D000068818:Cetuximab; C000607322:N-(2-amino-3-(para-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N,N',N',N'-pentaacetic acid; D012538:Scandium