Synthesis of 6-18F-Py-AMD3465 and the microPET/CT imaging of this agent in mice bearing A549 tumor

Abstract

Objective To synthesize 6-18F-Py-AMD3465, to investigate its biodistribution in mice and to perform the microPET/CT imaging on mice bearing human lung cancer cell (A549). Methods AMD3465 quaternary ammonium salt precursor was directly labeled with 18F, then 6-18F-Py-AMD3465 was synthesized through nucleophilic reaction, hydrolysis, neutralization and the product was purified using HPLC. The labeling yield and radiochemical purity were analyzed by HPLC. Fifteen Kunming mice were injected with 5.55 MBq of 6-18F-Py-AMD3465 and sacrificed at 5, 20, 40, 60 and 120 min postinjection. The selected tissues were harvested and weighed, and the radioactivity in the tissues was measured by an automated γ-spectrometer. The %ID/g was calculated. MicroPET/CT studies were performed on A549-bearing mice after injecting 6-18F-Py-AMD3465 through vena caudal. Paired t test was used. Results 6-18F-Py-AMD3465 was successfully synthesized with the labeling yield of (9.0±2.0)%, the total synthesis time was about 60 min, and the radiochemical purity was more than 98%. Biodistribution studies showed that the radiouptake was higher in the kidneys and bladder of normal mice, which demonstrated that 6-18F-Py-AMD3465 was mainly excreted through the kidneys. Biodistribution in A549-bearing mice was similar to that in normal mice. The tumor/muscle ratio at 40 min was 5.0, but the radiouptake of the tumor was still lower than that of the normal lung: (8.05±0.35) %ID/g vs (9.33±0.66) %ID/g; t=5.26, P<0.05. MicroPET/CT imaging showed that the high-uptake location of 6-18F-Py-AMD3465 in tumor-bearing mice was similar to the normal mice, and the tumor uptake reached the maximum level at 45 min post-injection (SUV 0.67). Conclusions 6-18F-Py-AMD3465 can be synthesized by a simple method. A lower uptake could be shown in the tumor compared to that in the lung and the tracer has limited diagnostic value for lung cancer. Key words: Receptors, chemokine; Antistatic agents; Isotope labeling; Flouorine radioisotopes; Tomography, emission-computed; Tomography, X-ray computed; Lung neoplasms; Mice