Time course of nodal enhancement with CT X-ray nanoparticle contrast agents: effect of particle size and chemical structure.

RATIONALE AND OBJECTIVES: Levels of CT enhancement in rabbit lymph nodes were followed with time after subcutaneous injection of four iodinated, insoluble nanoparticle contrast agents to provide experimental support for the hypothesis that clearance of these agents is related to the chemical structure of the agent itself. The impact of particle size was also studied. METHODS: Subcutaneous injections (2 x 0.25 mL) were made in the dorsum of rabbit paws with 15% suspensions of four nanoparticle contrast agents. Images were obtained at 4, 10, 24, 48, and 72 hours and 5, 7, and 14 days after injection. Average attenuation (in Hounsfield units [HU]), node volume, and total iodine uptake were estimated from the CT scans for each lymph node at each time point. RESULTS: All the agents provided adequate enhancement of both the popliteal and axillary lymph nodes of the rabbit (ie, > delta100 HU). Lymph node volume appears to be related to the persistence of enhancement, with long-lived agents demonstrating the greatest increase in size. The rate of clearance from the lymph nodes is related to the structure of the agent. CONCLUSIONS: Clearance of insoluble, iodinated nanoparticle contrast agents from lymph nodes can be modulated by changes in the structure of the agent itself. Using the same agent, smaller particles deliver material to the lymph nodes more quickly and clear more quickly.

Lymph node extraction of radiopaque nanoparticulates in the rabbit as measured in vivo with CT.

RATIONALE AND OBJECTIVES: The purpose of this study was to estimate in vivo extraction of lymphographic material in the popliteal node of the rabbit. MATERIALS AND METHODS: Serial quantitative computed tomography (CT) of target tissues in four legs of two rabbits was performed after subcutaneous injection of an improved lymphographic contrast agent. Massage was used as a lymphotrophic intervention. RESULTS: At 15 minutes, the mean change in Hounsfield units measured 815 in the popliteal node, 219 in afferent lymphatic vessels, and 127 in efferent lymphatic vessels. The nodal extraction of nanoparticulates from the lymph was approximately 55%. Nodal massage allowed the amount of nanoparticulate remaining in sinusoidal lymph to be estimated. CONCLUSION: Functional CT performed with timed studies, proper radiopaque materials, and physiologic interventions can depict in vivo lymphatic physiology under minimally invasive conditions.

Pulmonary delivery of nanoparticles of insoluble, iodinated CT X-ray contrast agents to lung draining lymph nodes in dogs.

Lung cancer continues to be a leading cause of death around the world. Staging of this disease is critically dependent upon the involvement or noninvolvement of the lymph nodes which drain the region of lung containing the lesion/tumor. Palpation, unenhanced CT, and lymph node excision (i.e., mediastinectomy) are currently used to ascertain the status of these regional draining lymph nodes. The work reported herein details the first efforts toward the pulmonary instillation of iodinated nanoparticles for contrast-enhanced CT of lung draining lymph nodes. The data reflect the impact of dose, time post instillation, and formulation (surfactant) upon the observed CT enhancement of the tracheobronchial lymph nodes of beagle dogs. In addition, initial safety is discussed with both macroscopic and microscopic observations. The results indicate that pulmonary instillation of small volumes of iodinated nanoparticles could be successfully used to aid staging of lung cancer by CT imaging.