Tumor Imaging Using Radiolabeled Matrix Metalloproteinase-Activated Anthrax Proteins

Area of Science:

• Biomedical Imaging
• Molecular Oncology
• Biotechnology

Background:

• Elevated matrix metalloproteinase (MMP) activity correlates with poor prognosis in various cancers.
• The anthrax protective antigen (PA) can be engineered for targeted delivery upon MMP cleavage.

Purpose of the Study:

• To develop and evaluate a novel noninvasive imaging strategy for detecting MMP activity in tumor tissues.
• To utilize a modified anthrax lethal toxin system for SPECT/CT imaging of MMPs in vivo.

Main Methods:

• Engineered MMP-cleavable PA (PA-L1) and radiolabeled anthrax lethal factor (LF) for SPECT imaging.
• Assessed PA-L1 activation, receptor expression, and MMP activity in cancer cell lines.
• Evaluated in vivo SPECT/CT imaging of radiolabeled PA-L1 and LF in tumor xenografts.

Main Results:

• PA-L1 activation correlated with MMP activity and anthrax receptor expression in cancer cells.
• Selective accumulation of radiolabeled PA-L1 and LF in MMP-positive MDA-MB-231 tumor xenografts was observed.
• Imaging signal was dependent on MMP-mediated PA-L1 activation, confirmed by inhibitor studies.

Conclusions:

• Radiolabeled anthrax toxin variants demonstrate potential for noninvasive imaging of MMP activity in tumors.
• This approach offers a promising tool for assessing tumor characteristics and guiding cancer therapy.