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

Elvas F, Vangestel C, Rapic S, Verhaeghe J, Gray B, Pak K, Stroobants S, Staelens S, Wyffels L - Mol Imaging Biol (2015)

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

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus

Histological and autoradiography analysis of tumor specimens. a Representative autoradiographic images, b hematoxylin and eosin staining, c cleaved caspase-3 immunostaining, and d TUNEL staining for vehicle-treated (upper panels) and irinotecan-treated (lower panels) tumors. Cells in brown were positive for caspase-3 and TUNEL stainings (arrows). Boxes indicate the areas where zoomed images were acquired. AU: arbitrary units.
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Fig6: Histological and autoradiography analysis of tumor specimens. a Representative autoradiographic images, b hematoxylin and eosin staining, c cleaved caspase-3 immunostaining, and d TUNEL staining for vehicle-treated (upper panels) and irinotecan-treated (lower panels) tumors. Cells in brown were positive for caspase-3 and TUNEL stainings (arrows). Boxes indicate the areas where zoomed images were acquired. AU: arbitrary units.

Mentions: Figure 6 shows representative autoradiographs and H&E-, CC3-, and TUNEL-stained sections of tumors from mice treated with vehicle and irinotecan. Autoradiographs show a heterogeneous uptake of [99mTc]duramycin in the tumors, which was higher in tumors treated with irinotecan (Fig. 6a). Compared with tumors from vehicle-treated mice, treatment with irinotecan caused cell shrinkage and condensed cytoplasm (Fig. 6b), formation of apoptotic bodies, increase in the number of CC3-positive cells (Fig. 6c; arrows) (9.5 ± 1.1 vs. 1.8 ± 0.4 in the control; p < 0.001), and DNA fragmentation, as assessed by an increase in the number of TUNEL-positive cells (Fig. 6d; arrows) (10.5 ± 1.6 vs. 3.5 ± 0.7 in the control; p = 0.006). Most importantly, this extensive apoptotic response was highly correlated with [99mTc]duramycin uptake in the tumors (CC3, r = 0.85 and p < 0.001, and TUNEL, r = 0.92 and p < 0.001). The distribution of the apoptotic cells in the tumors matched the distribution of [99mTc]duramycin radioactivity. In control tumors, cold spots colocalized with low number of apoptotic cells, whereas in treated tumors high number of apoptotic cells corresponded to hot spots with high radioactivity (Fig. 6; boxes).Fig. 6


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

Elvas F, Vangestel C, Rapic S, Verhaeghe J, Gray B, Pak K, Stroobants S, Staelens S, Wyffels L - Mol Imaging Biol (2015)

Histological and autoradiography analysis of tumor specimens. a Representative autoradiographic images, b hematoxylin and eosin staining, c cleaved caspase-3 immunostaining, and d TUNEL staining for vehicle-treated (upper panels) and irinotecan-treated (lower panels) tumors. Cells in brown were positive for caspase-3 and TUNEL stainings (arrows). Boxes indicate the areas where zoomed images were acquired. AU: arbitrary units.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig6: Histological and autoradiography analysis of tumor specimens. a Representative autoradiographic images, b hematoxylin and eosin staining, c cleaved caspase-3 immunostaining, and d TUNEL staining for vehicle-treated (upper panels) and irinotecan-treated (lower panels) tumors. Cells in brown were positive for caspase-3 and TUNEL stainings (arrows). Boxes indicate the areas where zoomed images were acquired. AU: arbitrary units.
Mentions: Figure 6 shows representative autoradiographs and H&E-, CC3-, and TUNEL-stained sections of tumors from mice treated with vehicle and irinotecan. Autoradiographs show a heterogeneous uptake of [99mTc]duramycin in the tumors, which was higher in tumors treated with irinotecan (Fig. 6a). Compared with tumors from vehicle-treated mice, treatment with irinotecan caused cell shrinkage and condensed cytoplasm (Fig. 6b), formation of apoptotic bodies, increase in the number of CC3-positive cells (Fig. 6c; arrows) (9.5 ± 1.1 vs. 1.8 ± 0.4 in the control; p < 0.001), and DNA fragmentation, as assessed by an increase in the number of TUNEL-positive cells (Fig. 6d; arrows) (10.5 ± 1.6 vs. 3.5 ± 0.7 in the control; p = 0.006). Most importantly, this extensive apoptotic response was highly correlated with [99mTc]duramycin uptake in the tumors (CC3, r = 0.85 and p < 0.001, and TUNEL, r = 0.92 and p < 0.001). The distribution of the apoptotic cells in the tumors matched the distribution of [99mTc]duramycin radioactivity. In control tumors, cold spots colocalized with low number of apoptotic cells, whereas in treated tumors high number of apoptotic cells corresponded to hot spots with high radioactivity (Fig. 6; boxes).Fig. 6

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

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus