More than seven years ago Albert J. Sinusas, MD, Professor of medicine, radiology and biomedical engineering, worked with a Team of engineers for development of an imageable polymer to prevent adverse remodeling after a heart attack when they accidentally discovered that when iodine, a contrast agent used for X-ray imaging, is packed into a nanoparticle, there is greater absorption of X-rays, potentially improving visibility.
Sinusas is head of the Yale Translational Research Imaging Center (Y-TRIC) turned to Tarek Fahmy, PhD, Associate Professor of Biomedical Engineering and Dongin (Donoven) Kim, PhD, now Assistant Professor at the University of Oklahoma, and one of the first Y-TRIC trainees to be supported by an NIH T32 grant for training in molecular and translational cardiovascular imaging with multiple modalities, which has just been extended for an additional five years.
The research team, led by Yale, found that CT contrast media such as iodine packaged in nanoparticles increased the absorption of X-rays by nearly an order of magnitude, improving sensitivity for imaging and disease characterization and reducing toxicity compared to potentially conventional ones Contrast media. Sinusas and the team of engineers received a patent for this concept on January 26, 2021 earlier this year.
“We found that when contrast agents are“ squeezed ”or clustered at the nanoscale (a few hundred nanometers), the overall contrast magnitude increases in a non-linear manner, which in short means that the scattering of electromagnetic waves is increased. We also found that this is not just an X-ray enhancement effect, but a general electromagnetic wave effect, that is, optical waves, radio waves, and others have been enhanced, ”said Fahmy.
It is believed that a nanoparticle is less than 200 nanometers in size. When these tiny particles are filled with iodine, they play an essential role in medical imaging using computed tomography (CT) scans. CT scans are based on computerized X-rays and are widely used in medical imaging. However, researchers agree that this diagnostic tool also carries a long-term risk of developing secondary cancer from ionizing radiation. Iodine-based compounds commonly used in conjunction with X-ray imaging can cause deterioration in renal function in patients with impaired renal function. Therefore, the use of an improved configuration of these contrast agents can enable diagnostic imaging with less radiation and a lower concentration of the contrast, thereby reducing overall toxicity.
When the contrast agent was entrapped or entrapped in nanoparticles, it exhibited various properties that improved CT contrast and improved imaging. More x-rays could be absorbed, which would reduce the toxicity associated with high concentrations of these contrast agents. The agents are made from units or polymers that provide increased blood flow and minimal vascular permeation, and possibly increased retention times when delivered into the heart muscle to improve repair after injury.
- Improved sensitivity: Increased absorption of X-rays leads to increased sensitivity for contrast detection and facilitates molecular targeted imaging.
- Lower likelihood of toxicity: allows a less iodine-reducing toxicity to be used with improved sensitivity
- Integration with FDA-approved nanomaterials: Incorporating iodine into FDA-approved polymers increases the likelihood of commercialization.
Exploring the diagnostic and therapeutic possibilities of medical image scanners
Sinusas is the author of over 250 peer-reviewed publications and has received multiple patents related to multi-modality cardiovascular imaging. On January 7, 2020, Sinusas received another patent for a catheter-based system with a retractable needle that he had developed together with Farhad Daghighian, PhD, as a minimally invasive method for the detection of molecularly targeted radiotracers for positron emission tomography (PET). This catheter-based technology could be used to control the delivery of iodinated theranostic polymers to prevent deleterious remodeling after a heart attack.
Sinusas and John Stendahl, MD, PhDThe also former T32 trainee is currently testing the use of contrast media on a standard basis to improve the imaging ability of bioresorbable stents and other future imaging technologies for the early detection of diseases and for therapy management.
Recently, Kim co-authored a paper that explored the benefits of nanoconfining. The manuscript "Nanoconfinement-mediated cancer therapy" was published in the archive for pharmaceutical research.
Source: Yale University