In vitro and in vivo magnetic resonance imaging with chlorotoxin-conjugated superparamagnetic nanoprobes for targeting hepatocarcinoma

Abstract

The present study aimed to assess the in vitro and in vivo magnetic resonance imaging (MRI) features of chlorotoxin (CTX)-conjugated superparamagnetic iron oxide (SPIO) nanoprobes. CTX-conjugated nanoprobes were composed of SPIO coated with polyethylene glycol (PEG) and conjugated with CTX. The nanoprobes were termed SPIO-PEG-CTX. MRI of the SPIO and SPIO-PEG-CTX solutions at a different concentration was performed with a 3.0-T MRI scanner (Philips Achieva 3.0T X Series; Phillips Healthcare, The Netherlands). Rabbit VX2 hepatocarcinoma was established by a traditional laparotomy method (injection of the tumor particles into the liver using a 15G syringe needle) following approval by the institutional animal care and use committee. Contrast-enhanced MRI of VX2 rabbits (n=8) was performed using the same MRI scanner with SPIO-PEG-CTX solutions as the contrast agent. Data were analyzed with calibration curve and a paired t-test. The SPIO-PEG-CTX nanoparticles were successfully prepared. With increasing concentrations of the solutions, the MRI signal intensity was increased at T1WI, but decreased at T2WI, which were the same as that for SPIO. Rabbit VX2 carcinoma appeared as a low MRI signal at T1WI, and high at T2WI. After injection of the contrast agent, the MRI signal of carcinoma was decreased relative to that before injection at T2WI (1,161±331.5 vs. 1,346±300.5; P=0.004<0.05), while the signal of the adjacent normal hepatic tissues was unchanged (480.6±165.1 vs. 563.4±67.8; P=0.202>0.05). The SPIO-PEG-CTX nanoparticles showed MRI negative enhancement at T2WI and a targeting effect in liver cancer, which provides the theoretical basis for further study of the early diagnosis of hepatocellular carcinoma.