Dual-Energy Micro-CT Functional Imaging of Primary Lung Cancer in Mice Using Gold and Iodine Nanoparticle Contrast Agents: A Validation Study

Abstract

PurposeTo provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT.MethodsPrimary lung tumors were generated in LSL-KrasG12D; p53FL/FL mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed–two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues.ResultsDual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R2 = 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements.ConclusionsDual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex vivo methods, CT-derived nanoparticle concentrations are accurate. This method could play an important role in lung tumor characterization by CT.

Imaging of Hsp70-positive tumors with cmHsp70.1 antibody-conjugated gold nanoparticles

“…7 Based on the k-edge, which is specific for the used substance, the contrast can be increased. Multimodal imaging is possible when several k-edge substances are used.…”

“…4,5 Due to the relatively high costs of gold, alternative materials, such as iodine, platinum, ytterbium, bismuth, and tantalum, are presently investigated in preclinical studies, 6 and iodine has been tested as a contrast agent in lung cancer patients. 7 For radiation therapy and for surgical removal of tumors in the brain, it is key to know the exact localization and size of a tumor. Tumor imaging with nanoparticles can be improved by coupling them…”

Engineering iodine-doped carbon dots as dual-modal probes for fluorescence and X-ray CT imaging

“…10 Consequently, the injection of contrast agents is necessary to achieve accurate and abundant information of region of interest. 11 Iodinated compounds are widely used as CT contrast agents in clinical applications due to their prominent photoelectric effect. 12 The cube of the high atomic number (Z=53) endows iodine with favorable X-ray attenuation property through photoelectric effect.…”

Gold Nanoparticles as X-Ray, CT, and Multimodal Imaging Contrast Agents: Formulation, Targeting, and Methodology

“…Ashton et al demonstrated tumor accumulation of PEGylated AuNP in an interesting study using dual-energy CT. AuNP were injected and allowed to accumulate in tumors for 2 days before the injection of iodine nanoparticles. The iodine particles acted as blood pool CA, while the AuNP provided contrast within the tumors [91]. PEGylated hollow AuNP are also capable of targeting tumors passively as shown by Park et al After injection into the tail vein, particle location was assessed using CT imaging and inductively coupled plasma (ICP) mass spectroscopy.…”