IOP Injection, A Novel Superparamagnetic Iron Oxide Particle MRI Contrast Agent for the Detection of Hepatocellular Carcinoma: A Phase II Clinical Trial

Abstract

BackgroundMRI is crucial in diagnosing hepatocellular carcinoma (HCC). Superparamagnetic iron oxide particles (SPIO) are liver‐specific contrast agents which enhance lesions in T2‐weighted images. Iron oxide nano‐particle m‐PEG‐silane (IOP) Injection, a newly developed SPIO, showed promising imaging effects and good safety profile in preclinical studies and in phase I clinical trial.PurposeTo evaluate the safety and clinical validity of IOP Injection as MRI contrast agent in diagnosing HCC.Study typeProspective.SubjectsA total of 52 subjects (61.6 ± 11.05 years, 45 males/7 females) with suspected HCC.Field Strength/Sequence1.5 T, T1‐weighted in/opposed phase, T2*‐weighted gradient echo, T2‐weighted fast spin echo, true fast imaging with steady‐state free precession.AssessmentAdverse effects and clinical monitoring were recorded throughout the 5‐day study. Two independent readers (M.G.H. with 30 years of experience, S.P.K. with 26 years of experience) made the diagnosis. The diagnostic performance of IOP‐enhanced MRI was evaluated with sensitivity and positive predictive value by comparing to the pathology reports from subsequent hepatic resection. The number of lesions with various sizes and degrees of differentiation detected by IOP‐enhanced MRI was assessed. The relative change in signal intensities over time was indirectly measured from acquired images.Statistical TestsSensitivity and positive predictive value were used to evaluate the diagnostic performance of IOP‐enhanced MRI. Prevalence‐adjusted and bias‐adjusted 𝜅 coefficient was used to assess the interreader variability.ResultsNo serious adverse event related to IOP Injection was found. IOP Injection enhanced the lesion‐to‐liver contrast ratio in T2*‐weighted images by 50.1% ± 4.8%. IOP‐enhanced MRI detected HCC with 100% sensitivity by subject and 96% sensitivity by lesion. IOP Injection visualized subtle vascular invasion as filling defect within vessels in true fast imaging with steady‐state free precession (TrueFISP) images.Data ConclusionIOP Injection was safe and efficacious as MRI contrast agent in diagnosing HCC in a limited group of subjects.Evidence Level2.Technical EfficacyStage 2.

Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy

“…Because IOPs are coated with PEG rather than high molecular weight iron dextran products, these new nanoparticles are expected to have a lower risk of immune complex anaphylaxis. Indeed, early phase clinical trials have demonstrated an excellent safety profile of this new agent in-human patients 10 . However, further studies in larger patient populations are needed before conclusions can be drawn regarding the rate of immunologic or nonimmunologic reactions to this new nanoprobe.…”

“…Indeed, early phase clinical trials have demonstrated an excellent safety profile of this new agent in-human patients. 10 However, further studies in larger patient populations are needed before conclusions can be drawn regarding the rate of immunologic or nonimmunologic reactions to this new nanoprobe.…”

“…This IOP is being developed as dedicated MRI contrast agent and tested in early clinical trials, with a favorable safety profile up to a dose 50 mg Fe/kg 10 . Thus far, this new IOP has been used for the detection of liver tumors 10 . However, the uptake of IOP in tumors outside of the liver has not been investigated.…”

Editorial for “IOP Injection, A Novel Superparamagnetic Iron Oxide Particle MRI Contrast Agent for the Detection of Hepatocellular Carcinoma: A Phase II Clinical Trial”

“…5,6,7 In this study, the authors present results from a phase II clinical trial of a new hepatobiliary contrast agent based on iron oxide nanoparticle m-PEG-silane (IOP). 8 Consequently, the aim of this study is to evaluate the effectiveness of the imaging strategy and identify potential side effects of the new contrast agent. The study population was comprised of 52 subjects (seven female) who had previously been diagnosed with HCC via dynamic multiphase CT or MRI.…”

“…In this study, the authors present results from a phase II clinical trial of a new hepatobiliary contrast agent based on iron oxide nanoparticle m‐PEG‐silane (IOP) 8 . Consequently, the aim of this study is to evaluate the effectiveness of the imaging strategy and identify potential side effects of the new contrast agent.…”