Radio-labelling and Micro-PET Study of 64Cu Labelled PnAO-1-(2-nitroimidazole) for Hypoxia Imaging†

doi:10.7503/cjcu20140438

Chem. J. Chinese Universities ›› 2015, Vol. 36 ›› Issue (1): 87.doi: 10.7503/cjcu20140438

• Organic Chemistry • Previous Articles Next Articles

Radio-labelling and Micro-PET Study of ⁶⁴Cu Labelled PnAO-1-(2-nitroimidazole) for Hypoxia Imaging^†

LUO Zheng¹, ZHU Hua¹, LIN Xinfeng¹, HONG Ye¹, XIAO Shaowen², ZHANG Qiang³, CHU Taiwei³, YANG Zhi^1,^*()

1. Department of Nuclear Medicine, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, 2. Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
3. College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China

Received:2014-05-08 Revised:2014-12-23 Online:2015-01-10 Published:2014-12-23
Contact: YANG Zhi E-mail:pekyz@163.com
Supported by:
Supported by the National Natural Science Foundation of China(Nos. 81071198, 81172083, 81371592) and the Beijing Municipal Natural Science Foundation, China(No. 7132040).

Abstract

Abstract:

Monitoring hypoxia is very important for tumor treatment, the ideal hypoxia imaging agents should have a relatively long half-life and specific to hypoxic cells. However, such an ideal imaging agent has not been developed until now. In order to develop an ideal imaging agent for monitoring hypoxia, nitroimidazole imaging agent PnAO-1-(2-nitroimidazole)[BMS181321] was synthesized and radiolabeled with ⁶⁴Cu for ⁶⁴Cu-BMS181321. The basic experimental process is as follows: the BMS181321 dissolved in sodium acetate buffer(pH=5.5) was added to the eluent of ⁶⁴CuCl₂, and the solution was stirred and placed at room temperature for 10 min. The labelling efficiency and radiochemical purity of ⁶⁴Cu-BMS181321 were all over 99%, determined by radio-HPLC. The ⁶⁴Cu-BMS181321 was stable in physiological saline for more than 15 h, which was a meaningful characteristic for clinical application. After quality control, 21.8 MBq of ⁶⁴Cu-BMS181321 was injected into human pancreatic cancer xenograft mouse models via tale vein. Positron emission tomography(PET) images were taken at 4 and 8 h after the injection. PET imaging in human tumor models was excellent compared with other PET hypoxia imaging agents. In brief, the research results suggest that ⁶⁴Cu-BMS181321 is potential for PET hypoxia imaging in clinical and should be further evaluated in clinic trial.

Key words: Nitroimidazole, 64Cu, Positron emission tomography, Hypoxia imaging

CLC Number:

O628
O652

TrendMD:

LUO Zheng, ZHU Hua, LIN Xinfeng, HONG Ye, XIAO Shaowen, ZHANG Qiang, CHU Taiwei, YANG Zhi. Radio-labelling and Micro-PET Study of ⁶⁴Cu Labelled PnAO-1-(2-nitroimidazole) for Hypoxia Imaging^†[J]. Chem. J. Chinese Universities, 2015, 36(1): 87.

Figures/Tables 4

Scheme 1 Radio-labelling of 64Cu-BMS181321

Fig.1 Influences of reaction time(A) and pH(B) on the labelling efficiency at 25 ℃ The yield(%) means the labelling efficiency of 64Cu-BMS181321.

Fig.2 In vitro stability of 64Cu-BMS181321 conjugated in different solutions a. 0.9% NaCl; b. NaAc buffer(pH=5.5).

Fig.3 PET images of 64Cu-BMS181321 at 4 h(A—C) and 8 h(D—F) after intravenious injection The white arrow represents hypoxic tumor, and the violet arrow represents necrotic tumor. (A, D) Transverse plane; (B, E) coronal plane; (C, F) sagittal plane.

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Radio-labelling and Micro-PET Study of ⁶⁴Cu Labelled PnAO-1-(2-nitroimidazole) for Hypoxia Imaging^†

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