RESUMO
Background and purpose:Integrinαvβ3 receptor plays an important role in promoting, sustaining and regulating the angiogenesis. It is overexpressed on neovascular endothelial cells and tumor cells. RGD peptide specifically binds to integrinαvβ3, which could evaluate growth status and invasiveness of tumor. This study aimed to investigate the biodistribution in healthy KM mice and micro PET/CT imaging in U87MG tumor-bearing mice of 18F-E[c(RGDfK)2]. Methods: 18F-E[c(RGDfK)2] was produced using an automated synthesis module via a simple one-step 18F-labeling strategy of the precursor 4-NO2-3-TFMBz-E[c(RGDfK)2]. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated at 0.5, 1, 2, 4 h post injection of the probe. Micro PET/CT images of U87MG tumor-bearing nude mice with or without 18F-E[c(RGDfK)2] blocking were acquired at each time point. Results: The labeling efficiency and radiochemical purity of 18F-E[c(RGDfK)2] were 10% and 98%, respectively. 18F-E[c(RGDfK)2] was excreted via renal route, with a high blood clearance. The other organs had background-level activity accumulation. At 1 h, the%ID/g of kidney, liver, intestine, muscle and blood was (1.02±0.16)%ID/g,(0.24±0.06)%ID/g, (0.35±0.03)%ID/g, (0.13±0.03)%ID/g and (0.11±0.03)%ID/g 18F-E[c(RGDfK)2] had initial high tumor uptake [(5.2±0.56)%ID/g] and good tumor-to-background contrast (5.36) at 1 h post injection. Tumor uptake for blocking group was lower than those without blocking, and T/M reduced to 1.57. Conclusion: 18F-E[c(RGDfK)2] appears a promising PET molecular imaging probe targeting integrin αvβ3, with high tumor uptake. It could be suitable for prognosis evaluation of integrin-positive tumor, selection of vascular targeting therapy and therapy effect monitoring.
RESUMO
Objective To investigate the application value of early evaluation and monitoring of 125Ⅰ interstitial implantation in a pancreatic cancer xeuograft.Methods Xenograft models were created by subcutaneous injection of Sw 1990 human pancreatic cancer cell suspensions into the right hind limbs of the immunodeficient BABL/c nude mice.The tumors size were about 8-10 mm after two weeks.The mice were randomly divided into 3 groups,including control group (n = 4) ,empty seed implantation group (n = 4)and 125Ⅰ implantation group (n = 4).Before treatment and one week after treatment,18F-FDG Micro-PET/CT scan was performed and then maximum standardized uptake values (SUVmax),mean standardized uptake values (SUVmean),tumor size and necrosis rate were measured.HE staining and TK1 immunohistochemistry examination were carried out in the paraffin-embedded sample.Results Before treatment the SUVmax and SUVmean values of three groups did not reach statistical significance.One week after treatment the SUVmax and SUV values of three groups were 3.53 + 1.20 and 0.57±0.26 vs.3.83±2.13 and0.59 ±0.24vs.0.29±0.23 and0.016±0.001,respectively,with a significant difference (F =7.62,P =0.01 ; F = 10.34,P =0.005).The SUVmax and SUVmean values of 125Ⅰ implant group were significantly lower than empty seed implant group and control group and were significantly lower than before treatment.Before treatment,tumor necrosis rate of three groups were not significantly different.Immunohistochemical staining found the TK1 positive staining index of three groups were respectively (64.25±1.71) % ,(62.25±2.22) % and (38.25±1.71) % with statistically significant difference (F =233.67,P < 0.001).The TK1 positive staining index of 125Ⅰ implant group was significantly lower than empty seed implant group and control group.The SUVmax values had some positive correlation with TK1 positive staining index (r = 0.85,P = 0.001).Conclusions 18F-FDG Micro-PET/CT may be useful as a noninvasive imaging modality to assess early response to 125Ⅰ seed brachytherapy in a pancreatic cancer xenograft.