Chlorotoxin-A Multimodal Imaging Platform for Targeting Glioma Tumors

Abstract

Chlorotoxin (CTX) is a 36-amino-acid disulfide-containing peptide derived from the venom of the scorpion Leiurus quinquestriatus. CTX alters physiology in numerous ways. It interacts with voltage gated chloride channels, Annexin-2, and matrix metalloproteinase-2 (MMP-2). CTX-based bioconjugates have been widely subjected to phase I/II clinical trials and have shown substantial promise. Many studies have demonstrated that CTX preferentially binds to neuroectodermal tumors, such as glioblastoma, without cross-reactivity to normal brain cells. With its ability to penetrate the blood-brain-barrier (BBB) and its tyrosine residue allows covalent conjugation with functional moieties, CTX is an attractive platform to explore development of diagnostic and therapeutic agents for gliomas. In this review, we outline CTX structure and its molecular targets, summarize molecular variations of CTX developed for glioma imaging, and discuss future trends and perspectives for CTX conjugates as a theranostic agent.

Keywords: chlorotoxin; glioblastoma; imaging modalities.

Figure 1

(A) The Israeli scorpion Leiurus quinquestriatu, from which its venom, chlorotoxin (CTX), is derived. (B) Three-dimensional structure of CTX reproduced from 1CHL PDB file [17], 1995, Biochemistry. (C) Visualization of IRDye 800CW-CTX targeting spontaneously develops medulloblastoma tumors in ND2:SmoA1 mice GBM. Left side: normal mouse brain. Right side: transgenic mouse model. Tumor location is marked using an orange arrow. Adapted with permission from Akcan et al. Reproduced from Reference [18], 2011, American Chemical Society.