PET imaging of apoptosis in tumor-bearing mice and rabbits after paclitaxel treatment with (18)F(-)Labeled recombinant human His10-annexin V

Haidong Qin; Ming-Rong Zhang; Lin Xie; Yanjie Hou; Zichun Hua; Minjin Hu; Zizheng Wang; Feng Wang

PET imaging of apoptosis in tumor-bearing mice and rabbits after paclitaxel treatment with (18)F(-)Labeled recombinant human His10-annexin V

Am J Nucl Med Mol Imaging. 2014 Dec 15;5(1):27-37. eCollection 2015.

Authors

Haidong Qin¹, Ming-Rong Zhang², Lin Xie², Yanjie Hou¹, Zichun Hua³, Minjin Hu⁴, Zizheng Wang¹, Feng Wang⁵

Affiliations

¹ Nanjing First Hospital, Nanjing Medical University 210006, China.
² Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Science Chiba 263-8885, Japan.
³ State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University Nanjing 210093, China.
⁴ Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc Changzhou 213164, China.
⁵ Nanjing First Hospital, Nanjing Medical University 210006, China ; State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University Nanjing 210093, China.

PMID: 25625024
PMCID: PMC4299778

Abstract

Monitoring response to chemo- or radiotherapy is of great importance in clinical practice. Apoptosis imaging serves as a very useful tool for the early evaluation of tumor response. The goal of this study was PET imaging of apoptosis with (18)F-labeled recombinant human annexin V linked with 10 histidine tag ((18)F-rh-His10-annexin V) in nude mice bearing an A549 tumor and rabbits bearing a VX2 lung cancer after paclitaxel therapy. (18)F-rh-His10-annexin V was prepared by conjugation of rh-His10-annexin V with N-succinimidyl 4-[(18)F]fluorobenzoate. Biodistribution was determined in mice by the dissection method and small-animal PET. Single-dose paclitaxel (175 mg/m(2)) was used to induce apoptosis in A549 and VX2 tumor models. (18)F-rh-His10-annexin V was injected into A549 mice and VX rabbits to acquire dynamic and static PET images 72 h after paclitaxel treatment. The uptake of (18)F-rh-His10-annexin V in apoptotic cells 4 h after induction was 6.45±0.52 fold higher than that in non-induced cells. High focal uptake of (18)F-rh-His10-annexin V was visualized in A549 (SUVmax: 0.35±0.13) and VX2 (0.41±0.23) tumor models after paclitaxel treatment, whereas lower uptake was found in the corresponding tumors before treatment (A549 SUVmax: 0.04±0.02; VX2: 0.009±0.002). The apoptotic index was 75.61±11.56% in the treated VX2 cancer, much higher than that in the untreated VX2 (8.03±2.81%). This study demonstrated the feasibility of (18)F-rh-His10-annexin V for the detection of apoptosis after chemotherapy in A549 and VX2 tumor models.

Keywords: Apoptosis; molecular imaging; recombinant human His10-annexin V; tumor response.