Characterization of [(99m)Tc]Duramycin as a SPECT Imaging Agent for Early Assessment of Tumor Apoptosis.

Abstract

PURPOSE:

We investigated the usefulness of [(99m)Tc]duramycin for monitoring early response to cancer therapy in mice, with an eye towards clinical translation.

PROCEDURES:

[(99m)Tc]Duramycin was injected in healthy CD1-/- mice to estimate human [(99m)Tc]duramycin radiation dose. [(99m)Tc]Duramycin single-photon emission computed tomography (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 [(99m)Tc]duramycin. [(99m)Tc]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, p < 0.001) and TUNEL (r = 0.92, p < 0.001) staining.

CONCLUSION:

[(99m)Tc]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.

• Authors: Filipe Elvas, Christel Vangestel, Sara Rapic, Jeroen Verhaeghe, Brian Gray, Koon Pak, Sigrid Stroobants, Steven Staelens, Leonie Wyffels
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 17 Issue 6 Pg. 838-47 (Dec 2015) ISSN: 1860-2002 [Electronic] United States
• PMID: 25896815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

• Bacteriocins
• Peptides
• duramycin
• Technetium

Topics

• Animals
• Apoptosis
• Bacteriocins (administration & dosage, chemistry, pharmacokinetics)
• Female
• Mice
• Mice, Nude
• Neoplasms, Experimental (diagnostic imaging, metabolism, pathology)
• Peptides (administration & dosage, chemistry, pharmacokinetics)
• Technetium (administration & dosage, chemistry, pharmacokinetics)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)