Comparison of Rhenium and Iodine as Contrast Agents in X-Ray Imaging.

Purpose: The majority of X-ray contrast agents (XCA) are made with iodine, but iodine-based XCA (I-XCA) exhibit low contrast in high kVp X-rays due to iodine's low atomic number (Z = 53) and K-edge (33.1 keV). While rhenium is a transition metal with a high atomic number (Z = 75) and K-edge (71.7 keV), the utilization of rhenium-based XCA (Re-XCA) in X-ray imaging techniques has not been studied in depth. Our study had two objectives: (1) to compare both the image quality and the absorbed dose of I- and Re-XCA and (2) to prepare and image a rhenium-doped scaffold. Procedures. I- and Re-XCA were prepared and imaged from 50 to 120 kVp by Micro-computed tomography (µCT) and digital radiography and from 120 to 220 kVp by planar X-ray imaging. The scans were repeated using 0.1 to 1.6 mm thick copper filters to harden the X-ray beam. A rhenium-doped scaffold was prepared via electrospinning, used to coat catheters, and imaged at 90 kVp by µCT. Results: I-XCA have a greater contrast-to-noise ratio (CNR) at 50 and 80 kVp, but Re-XCA have a greater CNR at >120 kVp. The difference in CNR is increased as the thickness of the copper filters is increased. For instance, the percent CNR improvement of rhenium over iodine is 14.2% with a 0.6 mm thick copper filter, but it is 59.1% with a 1.6 mm thick copper filter, as shown at 120 kVp by µCT. Upon coating them with a rhenium-doped scaffold, the catheters became radiopaque. Conclusions: Using Monte Carlo simulations, we showed that it is possible to reduce the absorbed dose of high kVp X-rays while allowing the acquisition of high-quality images. Furthermore, radiopaque catheters have the potential of enhancing the contrast during catheterizations and helping physicians to place catheters inside patients more rapidly and precisely.

Radioembolization of Hepatocellular Carcinoma with Built-In Dosimetry: First in vivo Results with Uniformly-Sized, Biodegradable Microspheres Labeled with 188Re.

A common form of treatment for patients with hepatocellular carcinoma (HCC) is transarterial radioembolization (TARE) with non-degradable glass or resin microspheres (MS) labeled with 90Y (90Y-MS). To further simplify the dosimetry calculations in the clinical setting, to have more control over the particle size and to change the permanent embolization to a temporary one, we developed uniformly-sized, biodegradable 188Re-labeled MS (188Re-MS) as a new and easily imageable TARE agent. Methods: MS made of poly(L-lactic acid) were produced in a flow focusing microchip. The MS were labeled with 188Re using a customized kit. An orthotopic HCC animal model was developed in male Sprague Dawley rats by injecting N1-S1 cells directly into the liver using ultrasound guidance. A suspension of 188Re-MS was administered via hepatic intra-arterial catheterization 2 weeks post-inoculation of the N1-S1 cells. The rats were imaged by SPECT 1, 24, 48, and 72 h post-radioembolization. Results: The spherical 188Re-MS had a diameter of 41.8 ± 6.0 µm (CV = 14.5%). The site and the depth of the injection of N1-S1 cells were controlled by visualization of the liver in sonograms. Single 0.5 g tumors were grown in all rats. 188Re-MS accumulated in the liver with no deposition in the lungs. 188Re decays to stable 188Os by emission of ߯ particles with similar energy to those emitted by 90Y while simultaneously emitting γ photons, which were imaged directly by single photon computed tomography (SPECT). Using Monte Carlo methods, the dose to the tumors was calculated to be 3-6 times larger than to the healthy liver tissue. Conclusions:188Re-MS have the potential to become the next generation of ߯-emitting MS for TARE. Future work revolves around the investigation of the therapeutic potential of 188Re-MS in a large-scale, long-term preclinical study as well as the evaluation of the clinical outcomes of using 188Re-MS with different sizes, from 20 to 50 µm.

Utilization of nanoparticles as X-ray contrast agents for diagnostic imaging applications.

Among all the diagnostic imaging modalities, X-ray imaging techniques are the most commonly used owing to their high resolution and low cost. The improvement of these techniques relies heavily on the development of novel X-ray contrast agents, which are molecules that enhance the visibility of internal structures within the body in X-ray imaging. To date, clinically used X-ray contrast agents consist mainly of small iodinated molecules that might cause severe adverse effects (e.g. allergies, cardiovascular diseases and nephrotoxicity) in some patients owing to the large and repeated doses that are required to achieve good contrast. For this reason, there is an increasing interest in the development of alternative X-ray contrast agents utilizing elements with high atomic numbers (e.g. gold, bismuth, ytterbium and tantalum), which are well known for exhibiting high absorption of X-rays. Nanoparticles (NPs) made from these elements have been reported to have better imaging properties, longer blood circulation times and lower toxicity than conventional iodinated X-ray contrast agents. Additionally, the combination of two or more of these elements into a single carrier allows for the development of multimodal and hybrid contrast agents. Herein, the limitations of iodinated X-ray contrast agents are discussed and the parameters that influence the efficacy of X-ray contrast agents are summarized. Several examples of the design and production of both iodinated and iodine-free NP-based X-ray contrast agents are then provided, emphasizing the studies performed to evaluate their X-ray attenuation capabilities and their toxicity in vitro and in vivo.

Uniform polymer microspheres: monodispersity criteria, methods of formation and applications.

For many applications, polymer microspheres (MS) should possess a monodisperse size distribution. With such uniformity they are able to deliver precise amounts of drug per MS, optimize the release kinetics of an encapsulated drug, obtain repeatable in vivo biodistributions to different organs and tissues, and obtain the maximum protection of (protein) drugs from degradation. This review classifies monodisperse polymer MS according to their methods of production and gives examples of the formation of uniform MS and their applications in the medical field. In the literature, the term 'monodisperse' is often used inaccurately, and this article attempts to rectify this by clearly defining monodispersity in terms of the coefficient of variation and the polydispersity index, the two statistical quantities most frequently used to describe the size distribution of MS.