MicroPET and biodistribution of 68Ga-labeled human epidermal growth factor receptor 2 binding affibody imaging probe
10.3760/cma.j.cn321828-20191011-00221
- VernacularTitle:68Ga标记HER2亲和体显像剂的microPET显像及生物分布
- Author:
Lizhen WANG
1
;
Yuping XU
;
Donghui PAN
;
Xinyu WANG
;
Junjie YAN
;
Min YANG
Author Information
1. 国家卫生健康委员会核医学重点实验室、江苏省分子核医学重点实验室、江苏省原子医学研究所，江苏省无锡市 214063
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2020;40(9):538-544
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To prepare a 68Ga labeled human epidermal growth factor receptor 2 (HER2) affibody 68Ga-1, 4, 7-triazacylononane-1, 4, 7-triacetic acid (NOTA)-maleimide (MAL)-Cysteine (Cys)-Glycine-Glycine-Glycine-Arginine-Aspartic acid-asparagine-HER 2: 342 affibody (GGGRDN-ZHER 2: 342)( 68Ga-MZHER), and evaluate its biodistribution and microPET characteristics. Methods:NOTA-MAL-Cys-GGGRDN-ZHER 2: 342 conjugate was labeled with 68Ga in one step. Radiochemical purity, radiolabeling yield and stability in vitro were analyzed. Normal mice ( n=24) were scarified at 15, 30, 60 and 120 min postinjection (1.85 MBq 68Ga-MZHER) to measure radioactive counts (percentage activity of injection dose per gram of tissue (%ID/g)) in main organs. Biodistribution and kinetics were evaluated by dynamic microPET in mice. Ovarian cancer (SKOV-3) models were established and microPET was performed at 30, 60 and 120 min postinjection of radiotracer. After administration of unlabeled Cys-ZHER 2: 342 peptide (10 mg/kg body weight) for 30 min, 68Ga-MZHER was injected into mice and PET images were acquired at 60 min postinjection. Region of interest (ROI) was drawn to access time-activity curve (TAC) in main organs and tumor. Six normal mice were used for the safety study. Results:68Ga-MZHER was synthesized in about 15 min with the yields more than 90%, and radiochemical purity more than 95%. The radiochemical purity was also determined to be more than 95% after being stored for 120 min at room temperature. Predominant uptake of 68Ga-MZHER was in the kidneys, and was cleared rapidly in normal tissues except the kidney. At 15 min postinjection, the renal uptake value was (106.36±15.74) %ID/g, then gradually increased with time, up to (145.15±28.04) %ID/g (60 min), and decreased to (86.12±22.75) %ID/g after 120 min postinjection. The blood pharmacokinetic of the probe in mice was fit with the two-compartment model. MicroPET imaging in mice bearing HER2 positive SKOV-3 tumors showed that the xenografts were clearly visualized with good contrast to normal tissue. The uptakes in tumors was determined to be (11.26±0.50), (12.27±1.13) and (12.65±0.89) %ID/g at 30, 60 and 120 min postinjection. Block experiment showed that the corresponding values decreased to (1.25±0.28) %ID/g at 60 min postinjection. Safety studies showed that after injection of 68Ga-MZHER for 30 d, the mice survived and no obvious abnormalities were observed in the main organs as shown in pathological results. Conclusions:68Ga-MZHER can be successfully labeled by one-step method. The 68Ga-MZHER probe owns the advantages of favorable imaging properties, convenient preparation, excellent stability, safety, rapid clearance in the blood, which support its application for further research.
