Stable Confinement of Positron Emission Tomography and Magnetic Resonance Agents Within Carbon Nanotubes for Bimodal Imaging

Abstract

Aims Simultaneous positron emission tomography/MRI has recently been introduced to the clinic and dual positron emission tomography/MRI probes are rare and of growing interest. We have developed a strategy for producing multimodal probes based on a carbon nanotube platform without the use of chelating ligands. Materials & methods Gd3+ and 64Cu2+ ions were loaded into ultra-short single-walled carbon nanotubes by sonication. Normal, tumor-free athymic nude mice were injected intravenously with the probe and imaged over 48 h. Results & conclusion The probe was stable for up to 24 h when challenged with phosphate-buffered saline and mouse serum. Positron emission tomography imaging also confirmed the stability of the probe in vivo for up to 48 h. The probe was quickly cleared from circulation, with enhanced accumulation in the lungs. Stable encapsulation of contrast agents within ultra-short single-walled carbon nanotubes represents a new strategy for the design of advanced imaging probes with variable multimodal imaging capabilities.

Encapsulation of α-Particle–Emitting225Ac3+Ions Within Carbon Nanotubes

“…Control experiments (free 225 AcCl in serum) showed no significant nonspecific retention of 225 Ac 3+ on the filter devices. These results indicate that a serum challenge may be used as a stripping procedure to purify the material by removing loosely bound 225 Ac 3+ ions that are not embedded within Gd 3+ ion clusters and encapsulated within the nanotube, as reported previously for US-tubes filled with 64 Cu (20). …”

“…Retention of the radioisotope within the nanotube reduces exposure to serum proteins and increases the area on the external sidewall that may be used for attaching targeting peptides or antibodies while retaining the therapeutic efficacy. Furthermore, the encapsulation of gadolinium within the carbon nanotubes has previously been shown to enhance MR imaging contrast (22), and a bimodal PET/MR contrast agent has been produced by trapping 64 Cu 2+ within Gd 3+ clusters (20). …”

Carbon Nanotubes as an Effective Opportunity for Cancer Diagnosis and Treatment

“…Using the second construct for the PET imaging, they obtained an approximately five-fold increase in specific activity, which improved the signal-to-noise ratio of the image [94]. While obtaining excellent results for cancer therapy with the first construct, it has to be noted that a single CNT could be designed to incorporate both the imaging [95] and therapeutic cargoes [96] onto the same platform.…”

“…They filled CNTs with Gd${}^{3+}$ and ${}^{64}$Cu${}^{2+}$, respectively, for MRI and PET systems. Despite that they did not test them on actual tumors, they proved platform stability over time in vivo and verified their accumulation mainly into lungs and liver [95]. This represents one example of the direction taken in the design of advanced imaging probes with variable multimodal imaging capabilities.…”

Positron emission tomography and nanotechnology: A dynamic duo for cancer theranostics

“…Furthermore, chelator-free radiolabeling of SWNTs has also been reported, whereby metal halide Na 125 I was filled in the nanotubes by direct covalent conjugation and capped off to prevent any leakage. [82] In further studies, alpha-emitters like 225 Ac 3+ [83] and beta-emitters like 64 Cu 2+ [84] along with Gd 3+ ions were stably loaded into the bores of the ultrashort nanotubes by simple sonication, and employed for radioimmunotherapy and PET/MR imaging, respectively. The strategy potentially protects the encapsulated radioisotopes from transmetallation, thereby preventing any leakage and consequent off-target toxicity in vivo .…”