Synthesis and biological evaluation of 18F-AlF-NOTA-c(CGRRAGGSC)

Objective To synthesize 18F-AlF-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-c(CGRRAGGSC), which could specifically bind to the α chain of interleukin (IL)-11 receptor (IL-11R), and evaluate its targeting potential to IL-11R-positive tumors. Methods Polypeptide c(CGRRAGGSC) was first coupled with NOTA and then labeled with 18F by AlF labeling method. The radiochemical purity and radiochemical yield of 18F-AlF-NOTA-c(CGRRAGGSC) were analyzed by high performance liquid chromatography, and the stability in vitro was evaluated. The tracer biodistribution in tumor-bearing mice (cell line SKOV3) was evaluated by the dynamic imaging with microPET 30 min, 1 h, 2 h after injection of 18F-AlF-NOTA-c(CGRRAGGSC). The tracer kinetics was performed in normal mice. Pharmacokinetics parameters were calculated using DAS2.0 software. Results The radiochemical purity of 18F-AlF-NOTA-c(CGRRAGGSC) was higher than 95% and the radiochemical yield was (30.0±7.4)%. It could be stably maintained in phosphate-buffered solution and plasma for at least 2 h. MicroPET imaging showed that 18F-AlF-NOTA-c(CGRRAGGSC) had a good affinity to SKOV3 tumor. The tumor/muscle ratios at 30 min, 1 h, 2 h after the injection of 18F-AlF-NOTA-c(CGRRAGGSC) were 6.26±2.98, 7.19±3.63 and 9.05±4.30, respectively. The tracer was cleared rapidly in blood and mainly excreted by the liver and kidneys. The T1/2α and T1/2β were (0.38±0.14) h and (2.64±0.28) h, respectively. Conclusions 18F-AlF-NOTA-c(CGRRAGGSC) is easy to be synthesized and has a good affinity to IL-11R-positive tumors. It will be a potential IL-11R-targeting imaging agent. Key words: Interleukin-11; Receptors, interleukin-11; Peptides, cyclic; Fluorine radioisotopes; Isotope labeling; Positron-emission tomography; Ovarian neoplasms; Mice, nude