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

被引：35

作者：

Elvas, Filipe ^{[1
,2
]}

Vangestel, Christel ^{[1
,2
]}

Rapic, Sara ^{[1
]}

Verhaeghe, Jeroen ^{[1
]}

Gray, Brian ^{[3
]}

Pak, Koon ^{[3
]}

Stroobants, Sigrid ^{[1
,2
]}

Staelens, Steven ^{[1
]}

Wyffels, Leonie ^{[1
,2
]}

机构：

[1] Univ Antwerp, Mol Imaging Ctr Antwerp, B-2020 Antwerp, Belgium

[2] Univ Antwerp Hosp, Dept Nucl Med, B-2650 Edegem, Belgium

[3] Mol Targeting Technol Inc, W Chester, PA USA

来源：

MOLECULAR IMAGING AND BIOLOGY | 2015年 / 17卷 / 06期

关键词：

Tc-99m; Duramycin; Preclinical dosimetry; Small-animal SPECT imaging; Chemotherapy; Apoptosis; HIS-ANNEXIN A5; CELL-DEATH; TC-99M-LABELED DURAMYCIN; CANCER; BIODISTRIBUTION; PHOSPHATIDYLETHANOLAMINE; PHOSPHATIDYLSERINE; IRINOTECAN; DOSIMETRY; DOMAIN;

D O I：

10.1007/s11307-015-0852-6

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

We investigated the usefulness of [Tc-99m]duramycin for monitoring early response to cancer therapy in mice, with an eye towards clinical translation. [Tc-99m]Duramycin was injected in healthy CD1-/- mice to estimate human [Tc-99m]duramycin radiation dose. [Tc-99m]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 x 10(-3) +/- 3.43 x 10(-4) mSv/MBq for non-purified and 3.19 x 10(-3) +/- 2.16 x 10(-4) mSv/MBq for purified [Tc-99m]duramycin. [Tc-99m]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. [Tc-99m]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.

引用

页码：838 / 847

页数：10

共 38 条

[1] The roles of therapy-induced autophagy and necrosis in cancer treatment [J].