A Nano Dose of Contrast: Tiny Particles, Big Impact

This essay will cover various pieces of research on the topic of how nanoparticles can replace traditional iodine-based contrast agents, particularly in CT and Fluoroscopy exams. While iodine contrast has played a valuable and reliable role in the world of radiographic imaging, the need for improvement in healthcare and medicine drives a curiosity of what could be the next best thing.

Literature Review

Metallic Nanoparticles for CT-guided Imaging of Tumors and their therapeutic Applications

This research explains the limitations of iodine contrast, gives reasons for needing improvement, and showcases the various experiments done to test various materials of nanoparticles which could be used for different imaging exams. Firstly, the need for a better contrast with better x-ray attenuation is necessary due to the many applications for its use. “High contrast imaging of the patient is critical for accurate and early diagnosis, and thereafter the elimination of the abnormality” (Gupta, 2023). Exams looking to diagnose blood clots, bone breaks, cancer, infections, and any cardiovascular diseases would benefit from a high attenuating contrast. Researchers have therefore looked at metallic nanoparticles as they show promising characteristics. The main attraction to metallic nanoparticles is their high Z numbers. The materials of interest in this research include gold, copper, iron, silver, platinum, holmium, tungsten, gadolinium, rhenium, lead, and molybdenum. According to data from this research, Gold has the highest atomic number at 79. It also has a k-absorption edge of 80.7 keV. On top of these qualities, gold nanoparticles can be engineered to be made biocompatible and can be made to have target specificity to organs or various tissues. The engineering of gold seems to be the biggest achievement of these experiments. For gold nanoparticles to be considered medically safe, various coatings were tested. The findings showed that coatings of 2-mercaptosuccinic acid (MSA) and Polyethylene glycol (PEG) enabled biocompatibility. This means gold could stay in the body for extended periods of time without causing adverse effects as iodine contrast can do in high quantities. On the topic of target specificity, gold nanoparticles coated with clostridium novyi-NT spores were able to be injected intratumorally and had successful germination in  hypoxic tissue. Final CT imaging was able to show accumulation in target spots. This was also seen in M-capped GNPs when targeting lymph nodes. These nanoparticles are made with mannan which acts as a stabilizing and reducing agent. When they were injected into mice, high-contrast CTs saw high values in the popliteal lymph nodes seven times greater because of effective diffusion. The other metals tested have their own benefits. Copper-based nanoparticles engineered with selenium were tested and had some added benefits to the body as these substances are biodegradable and necessary for energy production and aid in making DNA. Along with these benefits, these nanoparticles displayed an 8-hour half-life whereas iodine contrast stays in the desired anatomy for only a couple minutes. The copper nanoparticles were also able to be cleared naturally over time by the kidneys. This is important because particles that stay in the body unnecessarily can cause adverse effects.

There are many promising findings in this research. While this is exciting, further testing is needed to make sure there is complete safety and understanding of this technology. A concern with this research is that not every nanoparticle is able to make it to clinical trials. Nanoparticles that haven’t been tested therefore raise the concern of biological barriers and may cause toxicity. The body’s macrophages may reject the nanoparticles which would defeat the purpose of administering them in the body. Clinical trials also require a larger quantity than is typically produced to be effective. But, continuing this research of nanoparticles may allow them to become a part of CT exams, particularly when imaging cancerous tumors.

Comparative Evaluation of Gold Nanoparticles as Contrast Agent in Multimodality Diagnostic Imaging

In this research, scientists address the adverse effects iodine-based contrast agents can have on the human body and showcase the improved qualities that nanoparticles have. It also states how different modalities can benefit from nanotechnology implementation. Iodine can cause allergic reactions. “In addition, the potential of iodinated contrast-induced nephrotoxicity in high-risk patients have also been reported.” (Nabilah, 2024). All patients should have the ability to receive diagnostic quality images without concern for serious adverse effects. Allergic reactions can be life threatening. In fluoroscopy, angiography studies require a large quantity of iodine contrast to best visualize structures. “Furthermore, the extremely large volumes of iodine contrast needed may cause discomfort to the patient during administration process.” (Nabilah, 2024). Patients who are at risk for iodine contrast studies include those with previous reactions to iodine contrast, those with asthma, people with renal disease, heart disease, hyperthyroidism, severe dehydration, and even pregnancy. “Excessive iodine exposure may cause thyroid dysfunction in some individual with higher risk for pregnant and breastfeeding patients, as it may cross placenta barrier and excreted into breast milk.” (Nabilah, 2024). Studies have shown that metallic nanoparticles can solve this problem. “AuNPs have low toxicity effect and small size, are effortlessly transported by bloodstreams and are considered tolerable to be used in a high concentration of up to 1.4Au/kg.” (Nabilah, 2024).

Another driving force for this research also includes the search for better x-ray attenuation. With iodine, there are limitations due to surrounding tissues that get in the way of their ability to highlight structures. Along with this is the inability of iodine to reach cellular levels. This is necessary to find cancerous tumor cells. The experiments done in this research compare iodine contrast to gold nanoparticles and their performance under four different imaging modalities.  First, the two different contrast agents were prepared to have 5 different concentration levels of 3,5,10,15, and 20 millimoles. The experiments were then able to continue with CT imaging. The various concentration levels of contrast agents were able to be tested in a phantom model in the Siemens machine. Axial images were kept to have plenty of information about each sample in reference to the CT enhancement. Pictures were also taken at different energy levels of 80kVp, 100kVp, 120kVp, and 140kVp. Similarly, a Shimadzu was used as the fluoroscopy machine of choice. In this experiemnt, the various concentration levels of contrast were injected into a phantom and were irradiated under different fluoroscopy pulse modes at various energy levels of 50, 60, 65, 70, 75, 80, and 85kVp. What these tests were looking for was CNR. “CNR is a measurement method to study the capability of an imaging modality to differentiate radiographic structures.” (Nabilah, 2024). Results showed that the 15nm of AuNP had the best CNR values compared to iodine contrast across the different imaging modalities.

Polymeric Nanoparticles for drug Delivery: Recent Developments and Future Prospects

This research touches on the versatility and the customizations that are possible with nanotechnology. “Polymeric nanoparticles stand out as a key tool to improve drug bioavailability or specific delivery at the site of action. The versatility of polymers makes them potentially ideal for fulfilling the requirements of each particular drug-delivery system.” (Begines, 2020). Metallic nanoparticles greatly improve visibility of internal structures for exams such as CT and Fluoroscopy. The application of nanoparticles does not stop there. Researchers want to use nanoparticles to help deliver drugs to patients in the safest way possible. To come to this conclusion, various materials and coatings of nanoparticles were tested for ocular disease drug delivery as well as cancerous disease drug delivery. The WHO states 2.2 billion people have some sort of Ocular disease, and one billion cases could have been stopped with proper treatment. This statistic drove the desire to specifically test drug delivery systems (DDS) for ocular diseases. Testing was therefore done on Micelle nanoparticles for ocular delivery. The finding showed that PLGA/ PVA or poly lactic-co-glycolic acid and polyvinyl alcohol display great biocompatibility and biodegradability when delivering bevacizumad-loaded micelles to treat retinal and choroidal neovascularization. There was a short half –life which meant more intravitreal injections were required. While this aspect needs to be worked on, the pros included sustained release and the minimum concentration needed to completely block vascular endothelial growth factor for about two months of 500ng/mL endured in the vitreous humor. This was just one of the many materials tested for ocular DDS. With continued research, nanoparticles could become a staple in eye disease treatment.

This research was also interested in DDS for cancer treatment.  “ …cancer has become a leading cause of death in developed countries.” (Begines, 2020). The most common way to treat cancer is through chemotherapy. The issue with this is that it does take a toll on patients. This is because chemotherapy not only affects cancerous cells, but healthy cells as well. Researchers are therefore looking into the target specificity of nanoparticles. The goal is for nanoparticles to deliver drugs only to cancerous cells.  Nanoparticulate systems in use today are liposomes, albumin-based NPs, polymeric NPs and inorganic NPs. What was found is that polymers are biodegradable and biocompatible.

Now, DDS with the use of nanoparticles is not perfect. Some drawbacks are important to note. They have limited shape, chemistry, and electromagnetic properties that would lead to bad oral bioavailability and a couple other issues. As unfortunate as this sounds, hope remains because researchers are already working on new methods to correct these issues including the particulate replication in no wetting templates (PRINT). This would basically allow for more customizations and stabilization of the particles. This would help create better uptake of therapeutic drugs in the future.

Application of nanotechnology in medical diagnosis and imaging

This article also expresses how customizable nanoparticles are and how valuable this is to radiography as well as for therapeutic qualities. “Importantly, subtle variation in size or composition of the nanoparticles can result in great changes in their optical, magnetic, or electrical properties that allows unique possibility of multiplexing.” (Singh, 2022). Once again, the need for contrast that can give the best diagnostic pictures is crucial for patients. The work that has been put into testing various coatings and various materials for the use in diagnostic imaging has taken so much work and resources. Continued positive findings will be crucial for clinical implementation.

Summary

My paper has covered the topic of qualities of nanoparticles that would make them better contrast alternatives to traditional iodine-based contrast in diagnostic imaging. The research included helps showcase various promising qualities as well as some drawbacks. It gives extensive insight into the experiments done testing various metals of nanoparticles to look for better x-ray attenuation, to test for biocompatibility, as well as looking into their customizability with researchers also wanting to use nanoparticles for therapeutic treatments of various diseases.

Conclusion

Nanoparticles are a great discovery and will be a great addition to the medical and healthcare space. Experiments done to showcase their various qualities have been extensive. While some drawbacks exist, the ability to overcome these drawbacks will be seen in a few years’ time. Experiments will continue, and the hope is to begin doing trials on people and not just lab rats. Nanoparticles are used in so many different applications in the world, such as electronics, food packaging, and even skin care. It is a matter of time before integration into clinical spaces becomes widely seen. As a future radiologic technologist, I hope to see this technology in my career lifetime.

References

Begines, B., Ortiz, T., Pérez-Aranda, M., Martínez, G., Merinero, M., Argüelles-Arias, F., & Alcudia, A. (2020, July 19). Polymeric nanoparticles for drug delivery: Recent developments and future prospects. Nanomaterials (Basel, Switzerland). https://pmc.ncbi.nlm.nih.gov/articles/PMC7408012/#sec4-nanomaterials-10-01403

Gupta, D., Roy, I., & Ghandhi, S. (2023, July). Https://www.sciencedirect.com/science/article/abs/pii/S1047847720300046?via=ihub. Science Direct. https://www.med.upenn.edu/pmi/events/https-www-sciencedirect-com-science-article-abs-pii-s1047847720300046-via-3dihub

Nabilah Talik Sisin, N., Ab Rashid, R., Zaky Harun, A., Geso, M., & Nordiana Rahman, W. (2024, December). Comparative evaluation of gold nanoparticles as contrast agent in multimodality diagnostic imaging. ScienceDirect. https://www.sciencedirect.com/science/article/pii/S1687850724002632

Singh, A., & Amiji, M. M. (2022, January 4). Application of nanotechnology in medical diagnosis and imaging – sciencedirect. ScienceDirect. https://www.sciencedirect.com/science/article/abs/pii/S0958166921002445