ABSTRACT
Objective To prepare a specific integrin αvβ3 probe 18F-Al-1,4,7-triacetic acid-1,4,7-triazacyclononane-2-(4-amino benzyl) thioamide-(3,6,9-trioxaundecanoic acid-11-amide)-(glutamic acid-cyclo(arginine-glycine-aspartic acid-phenylalanine-lysine) dimeric peptide) (18 F-Al-NOTA-PRGD2) and evaluate its feasibility for PET imaging in papillary thyroid carcinoma (PTC).Methods 18F-Al-NOTA-PRGD2 was synthesized by a novel Al18F complex strategy.Human PTC tissues were implanted into nude mice.Immunohistochemistry staining was performed to detect αvβ3 expression in human PTC tissues,xenografts in mice and adjacent normal tissues respectively.18F-Al-NOTA-PRGD2 with or without blocking agent of PRGD2 was injected via the tail vein into tumor-bearing mice (n =5) for microPET imaging.The radioactivity uptake in the tumor and major organs were measured via ROI technology.Biodistribution studies were also performed in tumor bearing mice (n=15) 30,60,120 min postinjection respectively.The two sample t test was used for statistical analysis.Results The labeling yield of 18F-Al-NOTA-PRGD2 was over 45％ (no attenuation correction) and the radiochemical purity was above 95％.The integrin αvβ3 expression was observed in human PTC both in situ specimens and xenograft in mice,while no expression was shown in the adjacent normal tissues.MicroPET imaging revealed that tumors were clearly visible with good tumor-to-background contrast.The radioactive uptake by tumor was (2.81 ±0.35) ％ ID/g,(2.45±0.27) ％ID/g and (1.80±0.21) ％ID/g at 30,60 and 120 min postinjection,respectively.In the presence of unradiolabeled PRGD2,the corresponding tumor uptake decreased to (0.51±0.05) ％ID/g at 60 min postinjection.High tumor uptake was also shown in the biodistribution studies,which was (3.09±0.25) ％ID/g,(2.75±0.37) ％ID/g and (1.90±0.16) ％ID/g at 30,60 and 120 min postinjection,respectively.The results were consistent with the microPET imaging results (t=1.456,1.465 and 0.847,respectively,all P＞0.0.5).18F-Al-NOTA-PRGD2 was rapidly cleared in blood and muscles,and the tumor to blood and muscle uptake ratios were 6.15±0.45 and 7.86±0.56 respectively.Conclusions 18 F-Al-NOTA-PRGD2 could be labeled easily and quickly with good labeling yield and radiochemical purity.Overexpressed integrin αvβ3 in PTC can be proved by both immunostaining and microPET imaging.18F-A1-NOTA-PRGD2 PET imaging might be a novel in vivo method for investigation of molecular mechanism in PTC.