In vitro and in vivo detection of drug-induced apoptosis using annexin v-conjugated ultrasmall superparamagnetic iron oxide (Uspio): A pilot study

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

Research output: Contribution to journalArticle

Abstract

Purpose: To 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. Methods: Apoptotic 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. Results: The 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. Conclusion: A newly developed Annexin V-USPIO could have the potential for detection of drug-induced apoptosis.

Original languageEnglish
Pages (from-to)142-149
Number of pages8
JournalMagnetic Resonance in Medical Sciences
Volume18
Issue number2
DOIs
Publication statusPublished - 2019

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

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