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.

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.

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.

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.

Ovarian neoplasms; Receptor, epidermal growth factor; Gallium; Positron-emission tomography; Mice, nude