Abstract
1087
Objectives: Hypoxia is widely existed in solid tumor, the existence of hypoxia plays an important role in increasing the radio- and chemo- therapy resistance, as well as the risk of metastasis and poor prognosis. Accurate assessment of tumor hypoxia is essential for the selection of radiation doses radiotherapy to improve survival. In this study, we developed a novel HIF-1α (hypoxia inducible factor-1α) specific PET probe, Al18F-CLLFVY, which was different in mechanism from traditional tumor hypoxia imaging agent, 18F-FMISO and 64Cu-ATSM. Al18F-CLLFVY was prepared as scheme 1 with routine Al18F labeling method with the radiochemical yield of 27-35%, the radiochemical purity was over 99% and the specific activity of 11.8±1.2 GBq/μmol. It was stable in vitro for 6 h in saline and the elution solution. Al18F-CLLFVY was lipophilic with the log P value of 0.63±0.05 (n=3). Cell uptake study in A549 cell line showed higher uptake in cells pretreated with CoCl2 (1.80±0.22 %) than that in cells pretreated with saline (0.86±0.03%, P=0.002). In mice bearing S180, Al18F-CLLFVY was highly accumulated in gallbladder and cleared out, the uptake was 1.22±0.91 and 0.33±0.28 ID% at 5 min and 120 min p.i., respectively. Al18F-CLLFVY showed high initial accumulation in tumor but cleared out with time, the uptake in tumor was 2.01±0.24 ID%/g at 5 min p.i. and m0.69±0.25 ID%/g at 120 min p.i.. As the accumulation in muscle and blood was fast cleared out, the tumor-to-muscle and tumor-to-blood ratios were increased with time, the ratios were 3.45 and 3.63 at 120 min p.i., respectively. We developed A549 lung cancer tumor models and performed micro-PET imaging. Similar with the biodistribution data in mice bearing S180, Al18F-CLLFVY was accumulated in gallbladder, intestine and tumor. Compared with the result of 18F-FMISO in mouse bearing A549, Al18F-CLLFVY showed comparable uptake in tumor, but lower uptake in lung and abdominal organs. Which offered high contrast between tumor and background. When co-injected with nonradioactive cyclo-CLLFVY, the tumor was invisible while the uptake in gallbladder and intestine was similar with mouse without cyclo-CLLFVY. The in vitro and in vivo study showed Al18F-CLLFVY was HIF-1α specific and hold the potential for tumor hypoxia.