Negative CT Contrast Agents for the Diagnosis of Malignant Osteosarcoma.

Xianfu Meng,Wenbo Bu,Baoming Wang,Jiawen Zhang,Xiangming Fang,Hua Zhang,Yanyan Liu,Meng Zhang,Zhenwei Yao,Yan Wang

doi:10.1002/advs.201901214

Abstract

The current positive computed tomography (CT) contrast agents (PCTCAs) including clinical iodides, present high CT density value (CT‐DV). However, they are incapable for the accurate diagnosis of some diseases with high CT‐DV, such as osteosarcoma. Because bones and PCTCAs around osteosarcoma generate similar X‐ray attenuations. Here, an innovative strategy of negative CT contrast agents (NCTCAs) to reduce the CT‐DV of osteosarcoma is proposed, contributing to accurate detection of osteosarcoma. Hollow mesoporous silica nanoparticles, loading ammonia borane molecules and further modified by polyethylene glycol, are synthesized as NCTCAs for the diagnosis of osteosarcoma. The nanocomposites can produce H2 in situ at osteosarcoma areas by responding to the acidic microenvironment of osteosarcoma, resulting in nearly 20 times reduction of CT density in osteosarcoma. This helps form large CT density contrast between bones and osteosarcoma, and successfully achieves accurate diagnosis of osteosarcoma. Meanwhile, The NCTCAs strategy greatly expands the scope of CT application, and provides profound implications for the precise clinical diagnosis, treatment, and prognosis of diseases.

Highlights

We proposed a novel strategy of negative CT contrast agents (NCTCAs) for the precise diagnosis of solid tumors 2.1
HMSN@AB@PEG nanoprobes as NCTCAs could respond to the acidic microenvironment of tumors, and achieve sensitive detection of osteosarcoma
In vitro and in vivo experiments showed that HMSN@AB@PEG could rapidly generate H2 gas in the tumor area and significantly reduce the CT density value in tumor region

Summary

Results and Discussions

We proposed a novel strategy of negative CT contrast agents (NCTCAs) for the precise diagnosis of solid tumors 2.1. The similar phenomena was observed from HMSN@AB@ PEG nanoparticles responding to acid (Figure S9 and Video S2, Supporting Information), which demonstrated HMSN@AB@ PEG had the potential to release H2 as negative CT contrast agents in the acidic microenvironment of tumors. The CT contrast performance of free AB molecules was investigated, which showed analogous results with HMSN@AB@PEG (Figure S10, Supporting Information). While intravenous injection of HMSN@AB@PEG (Figure S14, Supporting Information), we observed the similar results that we could not differentiate bone from tumor through both of gray and pseudo-color images (transvers). We calculated the change of CT density value in rectangular ROI at two time points (Pre and 120 min) before and after intravenous injection of HMSN@ AB@PEG (Figure S22, Supporting Information). We knew the strategy of NCTCAs for diagnosis of osteosarcoma was practicable

The Biocompatibility In Vivo

Conclusion

Experimental Section

Conflict of Interest