A scale to measure MRI contrast agent sensitivity

Alvares, Rohan D. A.; Szulc, Daniel A.; Cheng, Hai‐Ling Margaret

doi:10.1038/s41598-017-15732-8

Cited by 26 publications

(24 citation statements)

References 41 publications

(26 reference statements)

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“…Once assessed for their biocompatibility, 18LPC/SPIONs were also injected in the tail vein of a healthy rat, chosen as a small animal model to evaluate their in vivo pharmacokinetics and applicability as negative contrast agents for MRI analyses (Figure 18d). This effect is typically evaluated with the transverse proton relaxation time (T 2 ) reduction or transverse proton relaxation rate (R 2 ) increase [255,256].…”

Section: Discussionmentioning

confidence: 99%

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

et al. 2019

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The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Among the various metal-containing drugs investigated thus far, ruthenium(III) complexes have emerged for their selective cytotoxic activity in vitro and promising anticancer properties in vivo, also leading to a few candidates in advanced clinical trials. Aiming at addressing the solubility, stability and cellular uptake issues of low molecular weight Ru(III)-based compounds, some research groups have proposed the development of suitable drug delivery systems (e.g., taking advantage of nanoparticles, liposomes, etc.) able to enhance their activity compared to the naked drugs. This review highlights the unique role of Ru(III) complexes in the current panorama of anticancer agents, with particular emphasis on Ru-containing nanoformulations based on the incorporation of the Ru(III) complexes into suitable nanocarriers in order to enhance their bioavailability and pharmacokinetic properties. Preclinical evaluation of these nanoaggregates is discussed with a special focus on the investigation of their mechanism of action at a molecular level, highlighting their pharmacological potential in tumour disease models and value for biomedical applications.

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Section: Discussionmentioning

confidence: 99%

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

et al. 2019

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“…Longitudinal relaxivities of GBCAs (r1 in mM −1 ·s −1 ) are in the range of 3–4 mM −1 ·s −1 at 1.5 T. 64 The typical concentration found in the DCN in the first month after repeated administration of gadodiamide is approximately 5–30 nmol/g (~5–30 μM assuming that 1g of tissue is close to 1 mL), 21 , 24 , 32 which is in the range of the lower limit of detection of MRI. 65 , 66 …”

Section: Methodological Aspects and Recommendations For Preclinical Smentioning

confidence: 99%

Methodological Aspects for Preclinical Evaluation of Gadolinium Presence in Brain Tissue

et al. 2018

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Gadolinium (Gd)-based contrast agents (GBCAs) are pharmaceuticals that have been approved for 30 years and used daily in millions of patients worldwide. Their clinical benefits are indisputable. Recently, unexpected long-term presence of Gd in the brain has been reported by numerous retrospective clinical studies and confirmed in preclinical models particularly after linear GBCA (L-GBCA) compared with macrocyclic GBCA (M-GBCA). Even if no clinical consequences of Gd presence in brain tissue has been demonstrated so far, in-depth investigations on potential toxicological consequences and the fate of Gd in the body remain crucial to potentially adapt the clinical use of GBCAs, as done during the nephrogenic systemic fibrosis crisis. Preclinical models are instrumental in the understanding of the mechanism of action as well as the potential safety consequences. However, such models may be associated with risks of biases, often related to the protocol design. Selection of adequate terminology is also crucial. This review of the literature intends to summarize and critically discuss the main methodological aspects for accurate design and translational character of preclinical studies.

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“…In fact, the most extensively investigated MnP, manganese (III) tetraphenyl porphyrin sulfonate (MnTPPS 4 ), exhibited no demetallation in vitro in human plasma for up to 9 days [ 13 ] and only about 1% degree of demetallation in vivo in liver and kidney up to 4 days post administration [ 14 ]. Additionally, MnPs have higher relaxivities than Gd-DTPA [ 12 , 15 ]; specifically, MnTPPS 4 has recently been shown to have a lower minimum detectable concentration and a greater sensitivity than Gd-DTPA in phosphate buffered saline [ 16 ]. Therefore, MnPs can achieve a positive contrast enhancement similar to Gd-DTPA but at lower doses, which reduces their systemic toxicity.…”

Section: Introductionmentioning

confidence: 99%

Manganese-porphyrin-enhanced MRI for the detection of cancer cells: A quantitative in vitro investigation with multiple clinical subtypes of breast cancer

et al. 2018

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Magnetic resonance imaging (MRI) contrast agents (CAs) are chemical compounds that can enhance image contrast on T1- or T2- weighted MR image. We have previously demonstrated the potential of MnCl2, a manganese-based CA, in cellular imaging of breast cancer using T1-weighted MRI. In this work, we examined the potential of another class of manganese-based CAs, manganese porphyrins (MnPs), for sensitive cellular detection of multiple clinical subtypes of breast cancer using quantitative MRI. Using a clinical 3.0-T MRI scanner, the relaxivities of two MnPs, MnTPPS4 and MnTPPS3NH2, and conventional Gd-DTPA (control) were measured in ultrapure water and their T1 contrast enhancement patterns were characterized in multiple clinical subtypes of breast cancer. The toxicity of the three CAs was evaluated in vitro. Compared to Gd-DTPA, both MnTPPS3NH2 and MnTPPS4 enabled a more sensitive multi-subtype detection of four breast cell lines at doses that posed no cytotoxic effects, with MnTPPS3NH2 producing the greatest positive enhancement. The superior T1 enhancement capabilities of MnPs over Gd-DTPA are statistically significant and are likely due to their greater cellular uptake and relaxivities. The results demonstrate that multiple clinical subtypes of breast cancer can be imaged on a 3.0-T MRI scanner using MnPs as T1 cellular CAs.

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A scale to measure MRI contrast agent sensitivity

Cited by 26 publications

References 41 publications

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

Methodological Aspects for Preclinical Evaluation of Gadolinium Presence in Brain Tissue

Manganese-porphyrin-enhanced MRI for the detection of cancer cells: A quantitative in vitro investigation with multiple clinical subtypes of breast cancer

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