Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging

Abstract

Standard clinical X-ray contrast agents are small iodine-containing molecules that are rapidly cleared by the kidneys and provide robust imaging for only a few seconds, thereby limiting more extensive vascular and tissue biodistribution imaging as well as optimal tumor uptake. They are also not generally useful for preclinical microCT imaging where longer scan times are required for high resolution image acquisition. We here describe a new iodine nanoparticle contrast agent that has a unique combination of properties: 20 nm hydrodynamic diameter, covalent PEG coating, 40 hour blood half-life, 50% liver clearance after six months, accumulation in tumors, and well-tolerated to at least 4 g iodine/kg body weight after intravenous administration in mice. These characteristics are unique among the other iodine nanoparticles that have been previously reported and provide extended-time high contrast vascular imaging and tumor loading. As such, it is useful for preclinical MicroCT animal studies. Potential human applications might include X-ray radiation dose enhancement for cancer therapy and vascular imaging for life-threatening situations where high levels of contrast are needed for extended periods of time.

Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice

“…Although approximate, values hitting as high as 4.5% iodine in the peripheral rim of the tumor indicate that the radiation dose delivered there may be multiplied by a factor of 8. These levels are higher than we previously reported for the U87 human glioma model 25 . An expectation is that this high DEF may then produce significant benefit in a radiotherapy treatment.…”

“…iodine nanoparticles. The synthesis and properties of the iodine nanoparticles were previously described 25 .…”

“…Other high atomic number nanoparticles are also being explored including gadolinium 21 , hafnium 22 , and bismuth 23 . Although gold nanoparticles appear to work well, they showed some disadvantages for human use: very poor whole body clearance 24 , long-term skin discoloration 25 , and high cost. We therefore constructed iodine nanoparticles that are very well tolerated with no demonstrable toxicity, have a pathway for biodegradation, a long blood half-life (40 h), an appropriate size for tumor uptake (20 nm), and are lower in cost 25 .…”

“…Although gold nanoparticles appear to work well, they showed some disadvantages for human use: very poor whole body clearance 24 , long-term skin discoloration 25 , and high cost. We therefore constructed iodine nanoparticles that are very well tolerated with no demonstrable toxicity, have a pathway for biodegradation, a long blood half-life (40 h), an appropriate size for tumor uptake (20 nm), and are lower in cost 25 . These were used previously to treat athymic nude mice with an advanced intracerebral human glioma resulting in two to threefold median life extensions 7 .…”

A literature review on multimodality molecular imaging nanoprobes for cancer detection

“…Wallyn and co-workers applied iodinated polymeric nanoparticles with strong X-ray attenuation capacity in the liver and spleen [24]. Similarly, a new polymer (triiodobenzene) iodine nanoparticle (INP) with a PEG coating was designed as a contrast agent for tumor loading by Hainfeld et al [25]. The iodine-based CT contrasts are either monomeric or dimeric forms of 1,3,5-triiodobenzene derivatives [26].…”