Abstract
1139
Background: Anaplastic thyroid cancer (ATC) comprises approximately 2% of all thyroid cancers, and its median survival rate remains poor due to its resistant to conventional therapy. Vascular endothelial growth factor receptor (VEGFR) targeted therapeutics loaded mesoporous silica nanoparticles (MSNs) represent a major advance for angiogenesis imaging and inhibition in lethal cancers. We aimed to assess whether 131I-labeled anti-VEGFR2 targeted MSNs would have antitumor efficacy in a ATC tumor-bearing nude mouse model.
Methods: The target binding of FRO ATC cells was observed by confocal microscopy. MSNs were radiolabeled with 131I by the Chloramine-T
Methods: The representative SPECT/CT images of FRO tumor-bearing mice were acquired at different time points after intratumoral injection with the respective drugs, and the survival probability and therapeutic efficacies including tumor size and body weight were investigated and monitored. Results: Immunofluorescence showed that both targeted and non-targeted MSNs could efficiently bind to FRO cells, and the targeting ability was enhanced via modifcation with anti-VEGFR2. The rate of 131I labeling was approximately 50-75%. SPECT/CT imaging showed radioactive accumulation in the Na131I group was rapidly excreted from the tumor at 2 day post-injection. Contrastly, the two groups with 131I-labeled nanoparticles had higher accumulation in the tumor tissue even at 2 week post-injection, and at 3 week after injection, the radioactivity in the targeted group was obviously stronger than that in the non-targeted group. On day 24 post-injection, the mean tumor volume in the Na131I and saline groups was 296.6± 24.2% and 278.3 ± 19.3%, respectively, compared with 198.7 ± 13.2% and 108.3 ± 12.3% in the non-targeted and targeted group on day 30 (all P<0.05). The body weight gradually declined in the Na131I and saline groups during the observed period, however, the other two nanoparticle groups had weight loss only at the first one week, which was regained by later time points, especially for the anti-VEGFR2 targeted group. The median survival time was 27, 25, 34 days in the saline, Na131I and non-targeted groups, respectively. Analysis with a log-rank test revealed that the treatment in the anti-VEGFR2 targeted group (median survival time, 41 days) resulted in better survival outcomes than the non-targeted group (P = 0.0047). Conclusions: The as-developed 131I-labeled anti-VEGFR2 targeted MSNs show promising results in ATC tumor-bearing mouse model. Our data support that such an approach may represent a novel therapeutic option for ATC.