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<i>In Vitro</i> and <i>In Vivo</i> Detection of Drug-induced Apoptosis Using Annexin V-conjugated Ultrasmall Superparamagnetic Iron Oxide (USPIO): A Pilot Study

4区 · 医学

Article

作者: Yamato, Mayumi ; Ichikawa, Kazuhiro ; Nohara, Satoshi ; Yoshise, Satoshi ; Ito, Yoshio ; Togao, Osamu ; Honda, Hiroshi ; Kato, Naoki ; Nishie, Akihiro ; Tamura, Chihiro

PURPOSETo investigate the binding potential of newly developed Annexin V-conjugated ultrasmall superparamagnetic iron oxide (V-USPIO) for detection of drug-induced apoptosis in vitro and in vivo.METHODSApoptotic cells induced by camptothecin were incubated with or without Annexin V-USPIO at a concentration of 0.089 mmol Fe/L in vitro. T₂ values of the two cell suspensions were measured by 0.47T nuclear magnetic resonance (NMR) spectrometer. Tumor-bearing mice were subjected to 1.5T MR scanner at 2 h after intraperitoneal injection of etoposide and cyclophosphamide. Following the pre-contrast T₁- and T₂-weighted imaging (0 h), the post-contrast scan was performed at 2, 4, 6 and 24 h after intravenous injection of Annexin V-USPIO (100 μmol Fe/kg). As a control, MRI was also obtained at 4 h after injection of USPIO without Annexin V. The ratio of tumor signal intensity (SI) on post-MRI for that on pre-MRI (Post/Pre-SI ratio) was calculated. After scanning, tumors were resected for pathological analysis to evaluate the distribution of iron and apoptotic cells.RESULTSThe suspension of apoptotic cells incubated with Annexin V-USPIO showed shorter T₂ value than that without it. On T₁-weighted imaging post/pre-SI ratio at 4 h after injection of Annexin V-USPIO showed 1.46, while after injection of USPIO without Annexin V was 1.17. The similar distribution of iron and apoptotic cells was observed in concordance with high signal intensity area on post-T₁-weighted imaging.CONCLUSIONA newly developed Annexin V-USPIO could have the potential for detection of drug-induced apoptosis.

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