Kit simplifies preparation of angiogenesis-scouting PET agent

Riding the wave toward expanded use of integrin-targeting angiogenic drugs, an agent requiring a complicated process of synthesis can now be generated in similar form with a simple kit. The agent, F-18 alfatide, is radiolabeled with integrin avb3-targeting peptides that bind to active tumor processes in squamous or adenomatous carcinoma--in this case of the lungs, according to research published this month in The Journal of Nuclear Medicine.

Weixing Wan, MBBS, from the Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, in Wuxi, China, and colleagues, elaborated on a single-step lyophilized kit for radiolabeling PRGD2 with fluorine-18 to generate F-18 alfatide and tested its efficacy for the detection of lung tumors. This novel agent is being presented as an alternative to the recently approved F-18 FPPRGD2, which requires multiple steps to synthesize.

“Noninvasive PET imaging of integrin avb3 has become an important tool for tumor diagnosis and treatment monitoring in both preclinical and clinical studies,” wrote Wan et al. “Currently, several F-18 labeled RGD peptides have been evaluated in clinical trials, and a more widespread use of PET imaging of integrin expression is expected in the near future. F-18 FPPRGD2 is one of the promising radiolabeled RGD peptides, with desirable pharmacokinetic properties for clinical noninvasive PET imaging of avb3 expression.”

F-18 FPPRGD2 has been shown to have a strong affinity to integrins, but without a more efficient method of synthesis, the promise of F-18 FPPRGD2 for diagnostic angiogenic and potential therapeutic antiangiogenic drugs might not be fully realized. The kit uses a fluoride–aluminum complex that simplifies production of the agent. The formulation was streamlined and optimized for F-18 activity, reaction time, temperature and pH balance. Results from this study provided a high yield of about 42.1 percent compared to previous reports of 5 to 25 percent yield.

“F-18 alfatide can be produced with excellent radiochemical yield and purity via a simple, one-step, lyophilized kit,” wrote the authors. “PET scanning with F-18 alfatide allows specific imaging of avb3 expression with good contrast in lung cancer patients. This technique might be used for the assessment of angiogenesis and for planning and response evaluation of cancer therapies that would affect angiogenesis status and integrin expression levels.”

For this study, nine male patients with lung cancer who had been diagnosed by biopsy, CT or F-18 FDG PET underwent F-18 alfatide PET imaging and one patient with tuberculosis received both PET and F-18 FDG imaging. Standardized uptake values were recorded at 30 minutes and one hour following injection. Expression of integrin was confirmed by staining intensity quantification and immunohistochemistry. Results showed that under optimal conditions the new method of synthesis required 20 minutes and provided a radiochemical purity rate of more than 95 percent. All tumors present in the nine patients were detected using F-18 alfatide.

“Our experience showed that the alfatide-labeling method is reliable, giving similar labeling yields from day to day. And after more than 100 kit labels, we haven’t encountered even a single failure,” the authors added. “By formulating peptides into kits, uncertainties about obtaining a successful labeled product can be avoided. Because of the simplicity of the method, an advantage is that additional studies can be easily performed in a single day.”

Additional clinical studies will need to be conducted with F-18 alfatide in order to secure its effectiveness and viability for antiangiogenic treatment and therapy monitoring to be used in conjunction with chemotherapy and radiotherapy for patients with a range of squamous or adenomatous carcinomas.