Molecular Ber-EP4 imaging towards theranostics for basal cell carcinoma

Authors

• B Dasgeb
• VM Diaz
• TJ Rosales
• DL Sackett
• JR Knutson
• AH Gandjbakhche
• IF Brownell

Abstract

Basal cell carcinoma (BCC) is the most common skin cancer. Differentiating benign from malignant lesions is by biopsy, incurring considerable cost and morbidity. Dermoscopy improves clinical examination; however, its utility is limited by subjective criteria, limitations of visual assessment, and lack of information beyond the surface. Deeper imaging with a wider field of view makes ‘macro optics’ essential for a non-invasive image-guided diagnosis of BCC. A more economic, time efficient and less invasive diagnostic technology is needed. BerEP4 - a pan-carcinoma biomarker – is expressed on 95% of BCCs. BerEP4 is not expressed on benign lesions mimicking BCC, and is expressed negligibly on normal skin epithelium. Therefore, BerEP4 is a desirable target for molecular imaging of BCC with low background noise. We used a near-infra-red (NIR) fluorophore (alexa750) labeled BerEP4 antibody (Ab) to image BerEP4 expressing tumors in Merkel and Basal cell carcinoma mice models. Sarcoma mice model (non-Ber-EP4-expressing) served as the negative control. Alexa750-anti-shigatoxin (an Ab with no target in mice) was the negative control for Ber-EP4 Ab. After IV injection of alexa750-BerEP4 we visualized Ber-EP4 expressing tumors (BCC and Merkel) in-vivo using the Bruker In-Vivo Xtreme multimodal imager. No signal was detected from sarcoma mice model or anti-shigatoxin. The ex-vivo fluorescent microscopy of excised tumors was consistent with in-vivo results. Our goal is bedside application. If successful, this technique may offer a rapid non-invasive-image-guided diagnosis, treatment and follow up for BCC, while reducing morbidities and cost. Such a platform can be applied to other skin malignancies.

Scientific Focus Area: Molecular Pharmacology

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