Multimodal VEGF-Targeted Contrast-Enhanced Ultrasound and Photoacoustic Imaging of Rats with Inflammatory Arthritis: Using Dye-VEGF-Antibody-Loaded Microbubbles.

Owing to the heavy health burdens from rheumatoid arthritis, a sensitive and objective imaging method is needed for early diagnosis and accurate evaluation of the disease. We aimed to fabricate vascular epithelial growth factor (VEGF)-targeted microbubbles (MBs) to evaluate the expression levels of VEGF within the inflammatory lesions of rats with adjuvant-induced arthritis (AIA) using a multimodal photoacoustic (PA)/ultrasound (US) imaging system. Fluorescein isothiocyanate-biotin double-labeled vascular endothelial growth factor receptor 2 antibodies and Cy5.5-biotin double-labeled VEGF2 antibodies were added to the avidin-labeled MBs to synthesize VEGF-targeted MBs. The antibodies could specifically bind to the MBs according to the flow cytometry and fluorescence imaging. In vitro experiments on the cellular uptake of the target MBs also validated the interaction of the VEGF antibodies and the MBs. Multimodal contrast-enhanced US (CEUS)/PA imaging was performed in sequence on the inflamed paws of the AIA rats with a single PA/US imaging system after the injection of the targeted MBs. The CEUS and PA signals were then quantified and verified by the pathologic results. A CEUS pattern of fast wash in and slow washout was observed in the AIA rats after injection of targeted MBs. Compared with AIA rats injected with unconnected VEGF antibodies and naked MBs, AIA rats injected with targeted MBs presented a higher peak intensity (p = 0.0079 and 0.0079 respectively) and a longer time to peak (p = 0.0117 and 0.0117, respectively). The PA signals were also significantly enhanced after injection of targeted MBs (p = 0.0112 and 0.0119, respectively), which was in accordance with the pathologic and immunohistochemical results. In conclusion, VEGF-targeted MBs can be used as agents for multimodal CEUS/PA imaging and to detect VEGF expression in the inflammatory lesions of AIA rats in vivo. This strategy may be useful in imaging evaluation of arthritis by identifying inflammation-related molecules in different imaging modes.

[Therapeutic evaluation of surgical procedure in treatment of secondary hyperparathyroidism].

OBJECTIVE: To analyze the short-term and long-term outcomes of the three operation methods in treatment of secondary hyperparathyroidism. METHODS: Clinical data of 88 patients who underwent parathyroidectomy for secondary hyperparathyroidism from October 2004 to October 2014 were reviewed retrospectively. Patients were divided into three subgroups, including subtotal parathyroidectomy (group I), total parathyroidectomy with autotransplantation (group II) and intraoperative 99Tc(m)-MIBI radioguided total parathyroidectomy with autotransplantation (group III). Their serum calcium, phosphorus, serum iPTH results in the pre-operation, short-term (≤ 6 months) and long term (> 6 months) of post-operation were collected and compared. The improvements of clinical symptoms together with the postoperative recurrence rate and the complication data were observed and analyzed. RESULTS: The symptoms of all patients were improved after the operation.The short-term postoperative serum calcium, serum iPTH and recurrence rate of Group I and group II were all not statistically significant. The short-term postoperative serum calcium, iPTH and recurrence rate of group III were significantly lower than those of group I and group II (P < 0.05). Postoperative serum phosphorus values of the three groups had no statistical difference. The operation time of group III was significantly shorter than that of group II ((77 ± 13) vs (108 ± 17) min, P < 0.05). The positive rates were more accurate in group III than in group II (98.5% vs 88.7%, P < 0.05). For the long term follow-up, the postoperative serum calcium, phosphorus, serum iPTH and recurrence rate of group I and group II were not statistically different. The postoperative recurrence rate of group III was lower than that of group I and group II (3.6% vs 31.6% and 21.4% respectively, P < 0.05). CONCLUSIONS: Total parathyroidectomy with autotransplantation has a good efficacy to treat secondary hyperparathyroidism. The intraoperative 99Tc(m)-MIBI radioguided total parathyroidectomy with autotransplantation can find the ectopic and supernumerary glands to improve the success rate of operation. And it also can permit omission of frozen section to reduce the operative time.In the postoperative follow-up, the recurrence rate is low, so it is a safe and effective treatment.