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Clearance Pathways and Tumor Targeting of Imaging Nanoparticles *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Most small molecular probes are small enough to pass the glomerular capillary walls and enter into urine in intact form if they have no interactions with serum proteins during circulation. During the first 24 h after intravenous (iv) injection, renal clearance efficiency of >50% injected dose (% ID) is widely observed in FDA-approved small molecular probes, such as gadolinium chelates for MRI (gadodiamide,15 gadopentetate dimeglumine,15 and gadoteridol16), iodinated contrast agents for CT(iohexol,17 iopamidol,17 and iopromide17), and 99mTc complexes for SPECT (99mTc-iron-ascorbate,18 99mTc-glucoheptonate,18 and 99mTc-MAG319) (Fig. 20.2). For clinical cancer diagnosis with PET imaging, [18F]fluoroglucose ([18F]FDG) is the most commonly used contrast agent and urinary excretion of [18F]FDG is ∼15% ID in 1.5 h postinjection (h p.i.).20 In the case of near-infrared fluorophores for in vivo fluorescence imaging used in preclinical cancer research, 44.0% ID of IRDye 800 CW and 86.0% ID of ZW800-1 were cleared from the body into urine by 4 h p.i.21 Because of such rapid and efficient urinary clearance, these small molecular probes after 4 h p.i. generally have low nonspecific accumulation in the vital organs such as kidney (the major organ involved in renal excretion), liver, and spleen. Only 0.3% ID of gadodiamide15 and 0.19% injected dose per gram of tissue (% ID/g) of IRDye 800 CW22 accumulated in the liver at 24 h p.i. The liver uptakes of 64Cu-DOTA,23 [18F]FDG24,and ZW800-121 were 0.33, 1.18, and 0.9% ID/g at 46, 12, 4 h p.i., respectively; their kidney uptakes were 0.35, 1.81, and 9.8% ID/g, respectively.
X-Ray, MRI, and Ultrasound Agents Basic Principles
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Michael F. Tweedle, Krishan Kumar, Michael V. Knopp
CIN was and remains a considerable concern in radiology. MRI scans were, from the beginning, capable of renal evaluation, and as the understanding of the CIN problem grew, it led in the late 1990s to the transfer of renally impaired patients (GFR < 30 mL/min × 1.73 m2) to MRI with MRCA evaluation to take advantage of the lower doses of renally excreted CA needed in MRI to reduce CIN risk. Especially, magnetic resonance angiography (MRA) was used at 0.2–0.3 mmol/kg, which is several times the usual dose used in the CNS examinations. In 2006, a rare disease of uncontrolled fibrosis, now known as NSF, was connected to the use of several of the linear Gd-chelates. The number of real cases will probably remain unknown, but 500 cases is a rough order estimate (Cowper 2001–2009). (Reference is made to the Cowper website for up-to-date information on NSF.) The disease occurs only in severely renal-impaired patients, and only following an MRI examination with certain MRCA. The disease is quite severe eventually, unless it resolves, leading to severely disabled joints, cachexia, and even death. The starting symptom is usually a small skin plaque or plaques on a lower extremity discovered anywhere from hours to years after exposure to the MRCA. Circumstantial evidence has accumulated that, in most opinions, now points to the release of free Gd, probably through transmetallation, as a necessary, but insufficient element of the disease’s etiology: (1) by a wide margin, gadodiamide has more unconfounded cases (i.e., only one agent used in the patient that develops NSF) relative to their market shares, compared to gadopentetate, a stronger and less labile chelate; (2) macrocyclic agents, the least labile, are very nearly devoid of cases relative to their market share; (3) studies in animals and humans demonstrate that linear chelating agents are more labile, and release more Gd, than macrocyclic ones; and (4) no new cases have developed since regulatory authorities contraindicated the aforementioned linear agents in susceptible patients, while the macrocyclic agents are still used in this patient population. Not all severely renal-impaired patients develop the disease after these linear MRCAs are administered, so some unknown element is also involved. One commonly discussed hypothesis is that freed Gd and some other unknown agent, event, or condition interferes with circulating fibrocytes, which in turn accelerates fibrosis (Vakil et al. 2009).
Gadolinium-based contrast agents: in vitro paraoxonase 1 inhibition, in silico studies
Published in Drug and Chemical Toxicology, 2021
Şükrü Beydemir, Cüneyt Türkeş, Ahmet Yalçın
In the present study, we carried out the in vitro drug–enzyme interaction studies by using purified PON1 enzyme. The enzyme was purified from human serum with simple methods including ammonium sulfate precipitation, IEX, and SEC at a short time. PON1 was obtained with a yield of 20.25%, and 3880.83 EU mg−1 protein specific activity (Table 2). The purified and subunit MW (43 kDa) of the enzyme were determined via SDS-PAGE. Subsequently, in vitro impacts of gadoteric acid, gadopentetic acid, gadoxetate disodium, and gadodiamide were tested in a dose-dependent manner, and IC50 values were 51.28 ± 0.14, 83.28 ± 0.28, 154.40 ± 0.56, and 285.80 ± 0.96 mM, respectively (Table 3, Figure 4). Ki constants were also calculated as 67.95 ± 0.60 mM, 104.97 ± 0.96 mM, 202.33 ± 1.75 mM, and 299.43 ± 2.64 mM, respectively (Table 3 and Figure 5). It was determined that gadoxetate disodium and gadodiamide were linked to the active site of the enzyme structure. The other drugs were seen being associated with a place outside the active region. While gadoxetate disodium and gadodiamide showed competitive inhibition, gadoteric acid, gadopentetic acid also had noncompetitive inhibition.
Gadolinium-based contrast agents – what is the evidence for ‘gadolinium deposition disease’ and the use of chelation therapy?
Published in Clinical Toxicology, 2020
Kerry A. Layne, David M. Wood, Paul I. Dargan
Recent radiological analyses and post mortem studies, however, have suggested that exposure to gadolinium-based contrast agents may result in gadolinium deposition in human brain and bone tissue in those patients with normal renal function [7–18]. In September 2017, the United States Food and Drug Administration (FDA) convened a Medical Imaging Drugs Advisory Committee meeting to review the emerging data related to gadolinium deposition in the brain and other body organs in patients with normal renal function. The team concluded that whilst current evidence shows that gadolinium is retained in human tissues post-exposure to gadolinium-based contrast agents, “for all or almost all of the millions of patients with normal renal function who have benefitted diagnostically from these drugs since 1988, the range of post-GBCA [gadolinium-based contrast agents] gadolinium retention probably falls below exposure thresholds that could induce grossly observable subacute/chronic adverse reactions” [6]. Subsequently, the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the FDA released new guidance in December 2017 advising healthcare professionals to aim to minimise requests for gadolinium-enhanced MRI scans unless diagnostic information is essential, with the MHRA also suspending the licences for the linear agents, gadodiamide (Omniscan) and intravenous gadopentetic acid (Magnevist) [19,20]. The European Medicines Agency similarly issued recommendations to restrict the use of some linear gadolinium agents used in MRI body scans and to suspend the authorisations of others [21].
Application of oxytocin in ultrasound-guided percutaneous microwave ablation for treatment of hypervascular uterine fibroids: a preliminary report
Published in International Journal of Hyperthermia, 2019
Yajie Fu, Qingliang Feng, Shihong Zhang, Yongjie Li
For MWA, a MWA therapeutic instrument was used (KY 2000, Nanjing Yigao Microwave System Engineering, Nanjing, P. R. China) with the following features: frequency 2450 MHz; low-temperature water circulation cooling system 14 G electrode needle; and front-end microwave radiator, 1.0 cm. The puncture guidance device was a CDU diagnostic instrument (GE LOGIQ-E9, GE Healthcare, Chicago, IL), probe model L2-5 MHz. Sulfur hexafluoride microbubbles (Bracco Imaging SpA, Milan, Italy) were used as an ultrasound contrast agent. The contrast agent was dissolved in 5.0 ml of sodium chloride solution (0.9%) w/v and after mixing, 2.4 ml of intravenous injection was used each time. The MRI equipment was from Centauri (1.5 T, Altech Medical Systems, Chengdu, P. R. China). The contrast agent gadodiamide (GE Healthcare, Chicago, IL), 0.3 mmol/kg at 2.0 ml/s, was used for enhanced MRI.