Negative CT Contrast Agents for the Diagnosis of Malignant Osteosarcoma

Abstract

and sensitivity. [4] Since the attenuation coefficient of X-ray is highly correlated with tissue density, [5] the current positive CT contrast agents (PCTCAs) exhibit high CT density value (CT-DV) and provide contrast enhancement in CT imaging. [6] However, CT with PCTCAs fails to accurately detect diseases that have similar X-ray attenuations to surrounding tissues, such as osteosarcoma, the most common primary bone malignancy in skeletal system disease. [7] For example, enhanced CT scanning can barely distinguish osteosarcoma from surrounding bones in high energy level images. This is because bones and PCTCAs of high-Z elements such as iodide, the lutecium-based upconversion nanoparticles, [8] can generate similar X-ray attenuations and then result in analogous high CT density between them. Consequently, PCTCAs suffer from insufficient ability to distinguish osteosarcoma from bones. Rationally reducing the density of osteosarcoma can enhance the contrast between osteosarcoma and bone, which is propitious to detect osteosarcoma sensitively.How can we reduce the density of osteosarcoma? A phenomenon in clinical CT lung inspection demonstrates the lung has lower CT density than the surrounding tissues. Briefly, in CT 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 H 2 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.

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

“…There are various examples of the suitability of using silica-based mesoporous nanomatrices for the delivery of antitumoral [144][145][146][147][148] or imaging agents [137,149,150] to bone cancer cells. Moreover, researchers have taken advantage of the features of the bone tumoral environment to design stimuli-responsive MSNs for the treatment of sarcomas.…”

Functional CT Contrast Nanoagents for the Tumor Microenvironment

“…Fortunately, our research group innovatively put forward with the concept of NCTCAs. [ 17 ] HMSN@AB@PEG nanoparticles as NCTCAs enabled specifically responding to the acidic microenvironment of tumor to generate hydrogen. They significantly reduced the CT density value of osteosarcoma area, which produced a remarkable contrast with the surrounding bone tissue, and then achieved accurate diagnosis of osteosarcoma (Figure 3B).…”

“…This commonly requires a large number of contrast agents, ≈0.5 mg mL −1 solution of gold nanoparticles (GNPs), to achieve such a CT contrast. [ 12,16 ] Recently, with the development of negative CT contrast nanoagents (NCTCAs) [ 17 ] and the availability of spectral CT, [ 18 ] it is possible to exploit functional CT contrast nanoagents (FCTNAs) for detecting the TME sensitively ( Scheme ). Therefore, we focus on FCTNAs in recent years, which are expected to monitor the TME sensitively and further achieve accurate diagnosis of tumor.…”

Understanding the In Vivo Fate of Advanced Materials by Imaging

“…For instance, a pH sensitive nanocomposite and an upconverting nanoparticle (UCNP) have been designed to enhance the CT contrast between bone and osteosarcoma, which are traditionally difficult to distinguish due to their similarly high CT density values. [19,20] The susceptibility to magnetization of iron-oxide forms the basis for their extensive use in MRI, [21] and more recently, magnetic particle imaging (MPI). [22] Iron-oxide is usually associated with negative-contrast when imaged with commonly used MRI sequences, which can be difficult to interpret when surrounded by anatomical structures also presenting with negative contrast signal (e.g., blood vessels).…”

“…[23] Furthermore, the magnetic properties of iron oxide materials can be sensitive to their physicochemical environment, for instance allowing processes such as cellular uptake and drug release to be monitored by MRI. We refer the reader to other excellent reviews on CT and MRI for further details, [24][25][26] including the use of materials incorporating other MRI-imageable isotopes (e.g., 19 F). [27] Ultrasound imaging provides unique advantages compared to other clinically relevant modalities, including low cost, no use of ionizing radiation, portability, and real-time imaging.…”