A novel Buthus martensii Karsch chlorotoxin derivative for glioma SPECT imaging

An increasing number of studies show the diagnostic and therapeutic potential of scorpion venoms and toxins in cancer, including malignant glioma that represents the most fatal primary brain tumors. Chlorotoxin (CTX) and a CTX-like peptide Buthus martensii Karsch chlorotoxin (BmK CT) derived from scorpion venoms, have been identified as glioma-specific agents for imaging and therapy. In this study, we designed and manufactured a new BmK CT derivative (BmK CT-D) according to the amino acid sequences of native CTX and BmK CT and investigated the possibility of 99mTc-labeled BmK CT-D as a single-positron emission computed tomography (SPECT) imaging agent for glioma diagnosis. The data indicated that the BmK CT-D peptide had good cytocompatibility, improved cellular uptake compared to BmK CT, and could be readily radiolabeled by 99mTc via 99mTc-tricarbonyl chemistry with high radiochemical yield and stability in vitro. Moreover, the formed 99mTc-BmK CT-D was able to be used as a probe for SPECT imaging of glioma cells in vitro and in tumor-bearing mice in vivo, indicating that the designed peptide is a promising targeting agent for tumor imaging.