RCC is a heterogeneous group of cancers with disparate genetic and molecular alterations underlying the various recognized histological subtypes
RCC is a heterogeneous group of cancers with disparate genetic and molecular alterations underlying the various recognized histological subtypes. HE staining revealed that 131I-4H7 significantly injures tumor cells. Our results suggest that 131I-4H7 is usually markedly absorbed by the tumor and did suppress the development of RCC xenografted tumors in nude mice, which might provide a new candidate for antibody-mediated targeted radiotherapy in human RCC. = 8) (A: 100, B: 100, C: 200, D: 400). Chemistry and radiochemistry 131I-4H7 and 131I-mIgG were prepared and the radiochemical purities of both were 95%. The stability of 131I-4H7 in PBS (pH 7.4) at 37C is shown in Physique ?Physique2.2. After 72 h of incubation, 95% of the 131I-4H7 and 131I-mIgG remained intact in PBS. Open in a separate window Physique 2 stability CCG-203971 of 131I-4H7 and 131I-mIgG in phosphate buffered saline (pH 7.4) at 37C for 1.0, 12, 24, 48, and 72 hTheir radiochemical purities were 95% and 95% of 131I-4H7 and 131I-mIgG remained intact in PBS after 72 h of incubation. Biodistribution studies Tissue distribution data for 131I-4H7 and 131I-mIgG in tumor-bearing nude mice are given as the percentage of administered activity per gram of tissue (%ID/g) (Physique ?(Figure3).3). biodistribution of injected 131I-4H7 and 131I-mIgG was examined in these mice. Open in a separate window Physique 3 Biodistribution of A. 131I-4H7 and B. 131I-mIgG in 786-0 tumor, heart, lung, liver, kidneys, and muscle after intravenous injection of 3.7 MBq CCG-203971 131I-4H7 or 131I-mIgG. C. Ratio of tumor to major organs (heart, lung, liver, kidneys, and muscle) based on the biodistribution data at 24-h post injection. Error bar was calculated as the standard deviation (= 6, mean SD). For 131I-4H7, the tumor uptake was decided to be 2.72 0.49, 2.32 0.77, 2.25 0.69, 3.32 0.46, 1.34 0.20, and 1.13 0.28% ID/g at 2.0, 4.0, 8.0, 24, 48, and 72 h, respectively. Its uptake rate peaked at 24 h, at which point the drug concentration in the tumor was 7.36-, 2.06-, 1.80-, 1.67-, and 2.78-fold higher than that in the muscle, CCG-203971 kidneys, liver, lung and heart, respectively (Determine ?(Figure3A).3A). For 131I-mIgG, the tumor uptake was 2.46 0.48, 2.21 1.73, 2.15 0.69, 2.67 0.29, 1.33 0.20, and 1.11 0.28% ID/g at 2.0, 4.0, 8.0, 24, 48, and 72 h, respectively. Its uptake rate also peaked at 24 h, at which point the drug concentration in the tumor was 5.02-, 1.58-, 1.39-, 1.29-, and 2.09-fold higher than that in muscle, kidneys, liver, lung and heart, respectively (Determine ?(Figure3B).3B). 131I-4H7 exhibited 7.39 1.11% ID/g liver uptake compared with 6.36 1.11% ID/g in 131I-mIgG at 2.0 h post-injection (Determine 3A-3B). 131I-4H7 showed 5.67 0.68% ID/g CCG-203971 of kidney uptake, which is higher than that of 131I-mIgG (4.64 0.68% ID/g) at 2.0 h pi (Determine ?(Physique3A3A and ?and3B).3B). It might be the reason that 4H7 metabolized mainly through the liver and kidneys. The nonspecific uptake in the muscle was at a very low level for both tracers. 131I-4H7 exhibited greater tumor uptake at the early time point and better tumor retention, indicating a longer circulation time. In addition, 131I-4H7 showed greater tumor CCG-203971 uptake compared to that of 131I-mIgG, and the 131I-4H7 tumor/kidney ratio of was significantly higher than that of 131I-mIgG (Physique ?(Physique3C).3C). Comparable tumor/muscle, tumor/liver, and tumor/heart ratios were observed for both 131I-4H7 and 131I-mIgG (Physique ?(Physique3C3C). Positron emission tomography /computed tomography (PET-CT) imaging studies The effect of 131I-4H7, 131I-mIgG, 131I, and saline on tumor xenograft growth in FKBP4 nude mice was evaluated by static PET-CT at different time points after intravenous injection. Rapid growth was observed in the groups treated with saline and 131I, in contrast, slow growth was observed in mice treated with 131I-4H7 and 131I-mIgG. Group treated with 131I-4H7 grew more slowly than those treated with 131I-mIgG (Physique ?(Physique44 and Supplementary Table 1). Open in a separate window Physique 4 Representative decay-corrected whole-body PET-CT images of the effect of drugs on tumor growthNude mice with renal cell carcinoma (RCC) xenografts were injected with.