RESEARCH ARTICLE Characterization of [99mTc]Duramycin as a SPECT Imaging Agent for Early Assessment of Tumor Apoptosis

Purpose: We investigated the usefulness of [99mTc]duramycin for monitoring early response to cancer therapy in mice, with an eye towards clinical translation. Procedures: [99mTc]Duramycin was injected in healthy CD1−/ − mice to estimate human [99mTc]duramycin radiation dose. [99mTc]Duramycin single-photon emission computed tomog-raphy (SPECT) imaging of apoptosis was evaluated in a mouse model of colorectal cancer treated with irinotecan and validated ex vivo using autoradiography, cleaved caspase-3, and TdT-mediated dUTP nick-end labeling (TUNEL) histology of the tumors. Results: The mean effective dose was estimated to be 3.74×10−3±3.43×10−4 mSv/MBq for non-purified and 3.19×10−3±2.16×10−4 mSv/MBq for purified [99mTc]duramycin. [99mTc]Duramycin uptake in vivo following therapy increased significantly in apoptotic irinotecan-treated tumors (p=0.008). Radioactivity in the tumors positively correlated with cleaved caspase-3 (r=0.85, pG0.001) and TUNEL (r=0.92, pG0.001) staining. Conclusion: [99mTc]Duramycin can be used to detect early chemotherapy-induced tumor cell death, and thus, may be a prospective candidate for clinical SPECT imaging of tumor response to therapy