Evaluation of nimotuzumab Fab2 as an optical imaging agent in EGFR positive cancers

• Published in: Scientific reports Vol. 13; no. 1; p. 10990
• Main Authors: Bernhard, Wendy, Barreto, Kris, Toledo, Darien, El-Sayed, Ayman, Jett, Kimberly A., Casaco, Angel, Fonge, Humphrey, Geyer, C. Ronald
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07-07-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4017; 692/53/2421; Cancer; Clinical trials; Epidermal growth factor receptors; Humanities and Social Sciences; Immunoglobulin G; Injection; multidisciplinary; Pepsin; Positron emission tomography; Probes; Science; Science (multidisciplinary); Surgery
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-37873-9

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.