In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents

Longo, Dario Livio; Michelotti, Filippo; Consolino, Lorena; Bardini, Paola; Digilio, Giuseppe; Xiao, Gang; Sun, Phillip Zhe; Aime, Silvio

doi:10.1097/rli.0000000000000217

Cited by 44 publications

(55 citation statements)

References 53 publications

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“…Although this simple estimate does not provide information on glomerular filtration rate or on renal blood flow, it was found to be correlated with the severity and with the evolution of the kidney damage. In addition, proof‐of‐concept studies have demonstrated that iopamidol and other radiographic agents can also provide perfusion estimates …”

Section: Discussionmentioning

confidence: 99%

“…37,38 In this study, renal pH values of the injured kidney significantly increased after AKI relative to the contralateral one, at both the ische- iopamidol and other radiographic agents can also provide perfusion estimates. 44,45 Nevertheless, a major limitation of all these approaches relies in the assessment of only one function of the kidneys, that is, their filtration capability, while the balance of the acid-base homeostasis has never been addressed. It is important to recognize that disordered acid-base homeostasis contributes to the progression of chronic kidney disease and to increased morbidity and mortality in dialyzed patients.…”

Section: Cest Renal Filtration Fraction Distinguishes Between Kidnementioning

confidence: 99%

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Noninvasive evaluation of renal pH homeostasis after ischemia reperfusion injury by CEST‐MRI

et al. 2017

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Acute kidney injury (AKI) in mice caused by sustained ischemia followed by reperfusion is associated with acute tubular necrosis and renal dysfunctional blood flow. Although the principal role of the kidney is the maintenance of acid-base balance, current imaging approaches are unable to assess this important parameter, and clinical biomarkers are not robust enough in evaluating the severity of kidney damage. Therefore, novel noninvasive imaging approaches are needed to assess the acid-base homeostasis in vivo. This study investigates the usefulness of MRI-chemical exchange saturation transfer (CEST) pH imaging (through iopamidol injection) in characterizing moderate and severe AKI in mice following unilateral ischemia reperfusion injury. Moderate (20 min) and severe (40 min) ischemia were induced in Balb/C mice, which were imaged at several time points thereafter (Days 0, 1, 2, 7). A significant increase of renal pH values was observed as early as one day after the ischemia reperfusion damage for both moderate and severe ischemia. MRI-CEST pH imaging distinguished the evolution of moderate from severe AKI. A recovery of normal renal pH values was observed for moderate AKI, whereas a persisting renal pH increase was observed for severe AKI on Day 7. Renal filtration fraction was significantly lower for clamped kidneys (0.54-0.57) in comparison to contralateral kidneys (0.84-0.86) following impairment of glomerular filtration. The severe AKI group showed a reduced filtration fraction even after 7 days (0.38 for the clamped kidneys). Notably, renal pH values were significantly correlated with the histopathological score. In conclusion, MRI-CEST pH mapping is a valid tool for the noninvasive evaluation of both acid-base balance and renal filtration in patients with ischemia reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

Section: Cest Renal Filtration Fraction Distinguishes Between Kidnementioning

confidence: 99%

Noninvasive evaluation of renal pH homeostasis after ischemia reperfusion injury by CEST‐MRI

et al. 2017

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“…Therefore, DR 1r and S r can provide images that are sensitive specifically to iohexol concentration and pH, respectively. The red line in Figure 3e is the best fit of Equation [4], which is used for pH calibration in the animal studies. k b , pH w , and Dv s in Equation [4] are fitted to be 0.98, 3.45 and 2977 s À1 , respectively.…”

Section: Discussionmentioning

confidence: 99%

“…The rat jugular vein was catheterized for intravenous injection. A 2‐mL 1.3‐M iohexol solution (in saline), according to a previous publication , was injected into each rat in 1 to 2 min. This corresponds for a 250‐g rat to a dose of approximately 4g I/kg body weight.…”

Section: Methodsmentioning

confidence: 99%

Spin‐lock imaging of exogenous exchange‐based contrast agents to assess tissue pH

Jiang

et al. 2017

Magnetic Resonance in Med

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Purpose: Some X-ray contrast agents contain exchangeable protons that give rise to exchange-based effects on MRI, including chemical exchange saturation transfer (CEST). However, CEST has poor specificity to explicit exchange parameters. Spin-lock sequences at high field are also sensitive to chemical exchange. Here, we evaluate whether spin-locking techniques can detect the contrast agent iohexol in vivo after intravenous administration, and their potential for measuring changes in tissue pH. Methods: Two metrics of contrast based on R 1r , the spin lattice relaxation rate in the rotating frame, were derived from the behavior of R 1r at different locking fields. Solutions containing iohexol at different concentrations and pH were used to evaluate the ability of the two metrics to quantify exchange effects. Images were also acquired from rat brains bearing tumors before and after intravenous injections of iohexol to evaluate the potential of spin-lock techniques for detecting the agent and pH variations. Results: The two metrics were found to depend separately on either agent concentration or pH. Spin-lock imaging may therefore provide specific quantification of iohexol concentration and the iohexol-water exchange rate, which reports on pH. Conclusions: Spin-lock techniques may be used to assess the dynamics of intravenous contrast agents and detect extracellular acidification. Magn Reson Med 79:298-305, 2018. V C 2017 International Society for Magnetic Resonance in Medicine.

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“…According to these considerations, researchers firstly turned their attention to already clinically approved contrast agents, such as iodinated contrast media, exploiting their high safety profile and FDA approval (Aime et al, 2005b;Longo et al, 2011). Consequently, radiographic agents have been exploited for assessing tumor microenvironment properties, including perfusion (Anemone et al, 2017;Longo et al, 2016b), acidosis (Chen et al, 2015;Jones et al, 2015;Longo et al, 2016a;Longo et al, 2014b;Sun et al, 2014) and for assessing renal functionality (Longo et al, 2013;Longo et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging

Longo

Moustaghfir

Zerbo

et al. 2017

International Journal of Pharmaceutics

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Chemical Exchange Saturation Transfer (CEST) approach is a novel tool within magnetic resonance imaging (MRI) that allows visualization of molecules possessing exchangeable protons with water. Many molecules, employed as excipients for the formulation of finished drug products, are endowed with hydroxyl, amine or amide protons, thus can be exploitable as MRI-CEST contrast agents. Their high safety profiles allow them to be injected at very high doses. Here we investigated the MRI-CEST properties of several excipients (ascorbic acid, sucrose, N-acetyl-d-glucosamine, meglumine and 2-pyrrolidone) and tested them as tumor-detecting agents in two different murine tumor models (breast and melanoma cancers). All the investigated molecules showed remarkable CEST contrast upon i.v. administration in the range 1-3ppm according to the type of mobile proton groups. A marked increase of CEST contrast was observed in tumor regions up to 30min post injection. The combination of marked tumor contrast enhancement and lack of toxicity make these molecules potential candidates for the diagnosis of tumors within the MRI-CEST approach.

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In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents

Abstract: The obtained results demonstrate that iohexol and ioversol, 2 commonly used radiographic compounds, can be used as MRI perfusion agents, particularly useful when serial images acquisitions are needed to complement CT information.

Cited by 44 publications

References 53 publications

Noninvasive evaluation of renal pH homeostasis after ischemia reperfusion injury by CEST‐MRI

Noninvasive evaluation of renal pH homeostasis after ischemia reperfusion injury by CEST‐MRI

Spin‐lock imaging of exogenous exchange‐based contrast agents to assess tissue pH

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging

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