Nanoengineered multimodal contrast agent for medical image guidance

Abstract

Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged <i>in vivo</i> residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 ± 7.1 mg/mL of iodine for iohexol and 9.8 ± 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 ± 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 ± 1.1% and 11.2 ± 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following <i>in vivo</i> administration, the contrast agent maintained a relative contrast enhancement of 81.4 ± 13.05 differential Hounsfield units (&#916;HU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 ± 144.2 differential signal intensity (&#916;SI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 ± 5.1 &#916;HU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 ± 41.4 &#916;SI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 ± 1.7 &#916;HU (94% decrease from the peak signal value achieved 3 minutes post-injection) and 461.7 ± 78.1 &#916;SI (60% decrease from the peak signal value achieved 5 minutes post-injection) in the kidney (cortex) of a New Zealand white rabbit. This multimodal contrast agent, with prolonged <i>in vivo</i> residence time and imaging efficacy, has the potential to bring about improvements in the fields of medical imaging and radiation therapy, particularly for image registration and guidance.