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Mol Imaging Biol. 2015 Dec;17(6):838-47. doi: 10.1007/s11307-015-0852-6.

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

Author information

1
Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
2
Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.
3
Molecular Targeting Technologies, Inc., West Chester, PA, USA.
4
Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium. leonie.wyffels@uza.be.
5
Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium. leonie.wyffels@uza.be.

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.

KEYWORDS:

99mTc; Apoptosis; Chemotherapy; Duramycin; Preclinical dosimetry; Small-animal SPECT imaging

PMID:
25896815
PMCID:
PMC4641155
DOI:
10.1007/s11307-015-0852-6
[Indexed for MEDLINE]
Free PMC Article

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