Development of silica-encapsulated silver nanoparticles as contrast agents intended for dual-energy mammography

• Published in: European radiology Vol. 26; no. 9; pp. 3301 - 3309
• Main Authors: Karunamuni, Roshan, Naha, Pratap C., Lau, Kristen C., Al-Zaki, Ajlan, Popov, Anatoliy V., Delikatny, Edward J., Tsourkas, Andrew, Cormode, David P., Maidment, Andrew D. A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2016; Springer Nature B.V
• Subjects: Animals; Breast cancer; Breast Neoplasms - diagnostic imaging; Contrast agents; Contrast Media; Contrast Media - administration & dosage; Contrast Media - chemistry; Contrast Media - pharmacokinetics; Diagnostic Radiology; Energy; Female; Humans; Imaging; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Internal Medicine; Interventional Radiology; Iodine; Mammography; Mammography - methods; Medical screening; Medicine; Medicine & Public Health; Mice; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neuroradiology; Phantoms, Imaging; Polyethylene glycol; Radiographic Image Enhancement - methods; Radiology; Signal-To-Noise Ratio; Silicon Dioxide; Silver; Subtraction Technique; Tumors; Ultrasound; United States > US; Nanoparticles; Silver; Gold; Mammography; Breast cancer; Dual-energy
• ISSN: 0938-7994; 1432-1084
• DOI: 10.1007/s00330-015-4152-y

Objective
Dual-energy (DE) mammography has recently entered the clinic. Previous theoretical and phantom studies demonstrated that silver provides greater contrast than iodine for this technique. Our objective was to characterize and evaluate in vivo a prototype silver contrast agent ultimately intended for DE mammography.
Methods
The prototype silver contrast agent was synthesized using a three-step process: synthesis of a silver core, silica encapsulation and PEG coating. The nanoparticles were then injected into mice to determine their accumulation in various organs, blood half-life and dual-energy contrast. All animal procedures were approved by the institutional animal care and use committee.
Results
The final diameter of the nanoparticles was measured to be 102 (±9) nm. The particles were removed from the vascular circulation with a half-life of 15 min, and accumulated in macrophage-rich organs such as the liver, spleen and lymph nodes. Dual-energy subtraction techniques increased the signal difference-to-noise ratio of the particles by as much as a factor of 15.2 compared to the single-energy images. These nanoparticles produced no adverse effects in mice.
Conclusion
Silver nanoparticles are an effective contrast agent for dual-energy x-ray imaging. With further design improvements, silver nanoparticles may prove valuable in breast cancer screening and diagnosis.
Key Points
•
Silver has potential as a contrast agent for DE mammography.
•
Silica-coated silver nanoparticles are biocompatible and suited for in vivo use.
•
Silver nanoparticles produce strong contrast in vivo using DE mammography imaging systems.