TY - JOUR T1 - Evaluation of anti-PEG gene mediated tumor therapy after pegylated liposomal drugs treatment in a hepatocellular carcinoma-bearing mouse model JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1585 LP - 1585 VL - 50 IS - supplement 2 AU - Mao-Chi Weng AU - Tien-Kuei Chang AU - Hsin-Ell Wang Y1 - 2009/05/01 UR - http://jnm.snmjournals.org/content/50/supplement_2/1585.abstract N2 - 1585 Objectives This study evaluated the gene-mediated tumor therapy of mice bearing hepatocellular carcinoma that express anti-PEG receptor (HCC36/AGP3-LDLr) and wild-type tumor (HCC36/WT) treated with vinorelbine-encapsulated pegylated liposomes (Lipo-VNB). Methods A novel 124I-4 arm-PEG-BH was prepared as a gene expression PET probe to target anti-PEG receptor expressed on HCC36/AGP3-LDLr cells. 111In-Lipo-VNB was prepared to evaluate the pharmacokinetics of Lipo-VNB. BALB/c nude mice were subcutaneously inoculated with HCC36/AGP3-LDLr and HCC36 cells in both lower flanks for 14 days. The cellular uptake, biodistribution, planar g imaging and therapeutic assay were performed. Results The labeling yield and radiochemical purity of 124I-4 arm-PEG-BH and 111In-Lipo-VNB were both > 90%. 124I-4 arm-PEG-BH m PET imaging, with a AGP3/WT ratio of about 5 at 24 h postinjection, was demonstrated a promising probe for anti-PEG receptor gene expression. In biodistribution study, the HCC36/AGP3-LDLr tumor uptake (12.68±4.33%ID/g) was two-fold higher than that of HCC36 tumor (5.92±0.55%ID/g) at 48 h after administration of 111In-Lipo-VNB. The planar g images also confirmed this finding. After Lipo-VNB treatment, the tumor growth inhibition (compared with original sizes) on HCC36/AGP3-LDLr (188±79%) was more obvious than HCC36 (446±124%) at 15, 17 d. Conclusions This study demonstrated that the gene-expression probe, 124I-4 arm-PEG-BH, selectively targeted the anti-PEG receptor on HCC36/AGP3-LDLr cells. Lipo-VNB were specifically accumulated in HCC36/AGP3-LDLr tumor and exerted highly anti-tumor effect. ER -