Coronary MR angiography using citrate‐coated very small superparamagnetic iron oxide particles as blood‐pool contrast agent: Initial experience in humans

Abstract

Purpose: To evaluate very small superparamagnetic iron oxide particles (VSOP-C184) as blood-pool contrast agent for coronary MR angiography (CMRA) in humans.Materials and Methods: Six healthy volunteers and 14 patients with suspected coronary artery disease underwent CMRA after administration of VSOP-C184 at the following doses: 20 mmol Fe/kg (4 patients), 40 mmol Fe/kg (5 patients), 45 mmol Fe/kg (6 healthy volunteers), and 60 mmol Fe/kg (5 patients). In healthy volunteers, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and vessel edge definition (VED) of contrast-enhanced CMRA were compared with non-contrast-enhanced CMRA. In patients, a per-segment intention-to-diagnose evaluation of contrast-enhanced CMRA for detection of significant coronary stenosis (!50%) was performed.Results: Three healthy volunteers (45 mmol Fe/kg VSOP-C184) and two patients (60 mmol Fe/kg VSOP-C184) had adverse events of mild or moderate intensity. VSOP-C184 significantly increased CNR (15.1 6 4.6 versus 6.9 6 1.9; P ¼ 0.010), SNR (21.7 6 5.3 versus 15.4 6 1.6; P ¼ 0.048), and VED (2.3 6 0.6 versus 1.2 6 0.2; P < 0.001) compared with non-contrast-enhanced CMRA. In patients, contrastenhanced CMRA yielded sensitivity, specificity, and diagnostic accuracy for detection of significant coronary stenosis of 86.7%, 71.0%, 73.1%, respectively.Conclusion: CMRA using VSOP-C184 was feasible and yielded moderate diagnostic accuracy for detection of significant coronary stenosis within this proof-of-concept setting.

Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization

“…20,21,[33][34][35] Along with these earlier observations, our experimental evidence of rapid accumulation of IV injected VSOP as a function of histopathologic parameters of plaque instability show that VSOP is a promising candidate for clinical MR angiography and vessel wall imaging; it might allow for the simultaneous evaluation of the arterial lumen and characterization of vessel wall pathologies, and thereby might help in identifying unstable atherosclerotic plaques.…”

“…The batch used in this study is identical to the batch used in the Phase I and Phase II clinical trials. 20,21 VSOP have been described in detail elsewhere. 20,22 Briefly, their basic properties are: a core diameter of 4 nm; hydrodynamic diameter of 7 nm; T1-relaxivity of 18.7; and T2-relaxivity of 30 L/(mmol × seconds) at 0.47 T. VSOP are stabilized with citrate, an anionic monomeric coating.…”

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

“…Numerous preclinical and several clinical studies describe their use both in MRA of individual vascular territories, such as pulmonary arteries [96], the aorta [80,97], coronary arteries [10,98,99], renal arteries [10], mesenterial and portal veins [100], hepatic veins [101], and the inferior vena cava [102], as well as in whole-body angiography of arteries and veins for assessing stenoses and thromboses [103]. Potential USPIO for clinical application are Supravist ® (SHU 555C, phase I, Bayer Healthcare Pharmaceuticals), AMI-227 (Sinerem ® , phase III), and VSOP-184 (phase I).…”

Biocompatibility of very small superparamagnetic iron oxide nanoparticles in murine organotypic hippocampal slice cultures and the role of microglia

“…So far, VSOP have been tested in vitro and in vivo by means of immortalized or primary cell cultures, animal models, and human probands. 2,17,28,44,45 In our view, further studies and assessments using OHSC are imperative. On the one hand, cell culture experiments exclude questions regarding VSOP interactions on the three-dimensional multicellular level.…”

“…[13][14][15] Although VSOP have been tested in clinical phase II trials, further assessment of cytotoxic effects is crucial. 16,17 SPIO can release free iron ions while degrading, subsequently altering cell cycle iron metabolism and potentially leading to an iron-catalyzed generation of reactive oxygen species, which increases mitochondrial dysfunction. 18,19 So far, the cytotoxic effects of SPIO have been controversially discussed in the literature.…”