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BMC Cancer. 2019 Oct 24;19(1):1000. doi: 10.1186/s12885-019-6238-4.

Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer.

Author information

1
Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.
2
Present address: Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, 1881 East Road, Houston, TX, 77054, USA.
3
Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.
4
Present address: Department of Nuclear Medicine and Molecular Imaging, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, 40161, Indonesia.
5
Oncology and Stem Cell Working Group, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, 40161, Indonesia.
6
Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan. hanaokah@gunma-u.ac.jp.
7
Project "Medical Radioisotope Application", Department of Radiation-Applied Biology Research, Takasaki Advanced Radiation Research Institute, Quantum Beam Advanced Research Directorate, National Institutes for Quantum and Radiological Science and Technology, 1233 Watanuki, Takasaki, 370-1292, Japan.

Abstract

BACKGROUNDS:

Overexpression of epidermal growth factor receptor (EGFR) has been established as a valid therapeutic target of non-small cell lung cancer (NSCLC). However, the clinical benefit of cetuximab as an EGFR-targeting drug is still controversial, partially due to the lack of effective means to identify suitable patients. This study aimed to investigate the potential of radiolabeled cetuximab as a non-invasive tool to predict cetuximab accumulation in NSCLC tumor xenografts with varying EGFR expression levels.

METHODS:

The NSCLC tumors in model mice were subjected to in vivo biodistribution study and positron emission tomography (PET) imaging 48 h after injection of either 111In- or 64Cu-labeled cetuximab. The EGFR expression levels of NSCLC tumors were determined by ex vivo immunoblotting.

RESULTS:

We found that tumors with high EGFR expression had significantly higher [111In]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [111In]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [64Cu]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [64Cu]Cu-DOTA-cetuximab allowed clear visualization of tumors.

CONCLUSION:

Our findings suggest that this immuno-PET imaging can be clinically translated as a tool to predict cetuximab accumulation in NSCLC cancer patients prior to cetuximab therapy.

KEYWORDS:

64Cu; Cetuximab; EGFR; Immuno-PET; Non-small cell lung cancer; Personalized medicine

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