Evaluation of nimotuzumab Fab 2 as an optical imaging agent in EGFR positive cancers.
Wendy BernhardKris BarretoDarien ToledoAyman El-SayedKimberly A JettAngel CasacoHumphrey FongeClarence Ronald GeyerPublished in: Scientific reports (2023)
Molecular-targeted imaging probes can be used with a variety of imaging modalities to detect diseased tissues and guide their removal. EGFR is a useful biomarker for a variety of cancers, because it is expressed at high levels relative to normal tissues. Previously, we showed the anti-EGFR antibody nimotuzumab can be used as a positron emission tomography and fluorescent imaging probe for EGFR positive cancers in mice. These imaging probes are currently in clinical trials for PET imaging and image-guided surgery, respectively. One issue with using antibody probes for imaging is their long circulation time and slow tissue penetration, which requires patients to wait a few days after injection before imaging or surgery, multiple visits and longer radiation exposure. Here, we generated a Fab 2 fragment of nimotuzumab, by pepsin digestion and labeled it with IRDye800CW to evaluate its optical imaging properties. The Fab 2 had faster tumor accumulation and clearance in mice relative to the nimotuzumab IgG. The fluorescent signal peaked at 2 h post injection and remained high until 6 h post injection. The properties of the Fab 2 allow a higher signal to background to be obtained in a shorter time frame, reducing the wait time for imaging after probe infusion.
Keyphrases
- high resolution
- clinical trial
- pet imaging
- positron emission tomography
- living cells
- computed tomography
- epidermal growth factor receptor
- tyrosine kinase
- small molecule
- gene expression
- type diabetes
- randomized controlled trial
- adipose tissue
- young adults
- coronary artery disease
- metabolic syndrome
- mass spectrometry
- ejection fraction
- drug delivery
- newly diagnosed
- insulin resistance
- skeletal muscle
- chronic kidney disease
- percutaneous coronary intervention
- open label
- high speed
- double blind