Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study
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Abstract
Purpose: To determine whether deposition characteristics of ferumoxytol (FMX) iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor lesion response to nanoliposomal irinotecan (nal-IRI). Experimental Design: Eligible patients with previously treated solid tumors had FMX-MRI scans before and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2* signal was used to calculate FMX levels in plasma, reference tissue, and tumor lesions by comparison with a phantom-based standard curve. Patients then received nal-IRI (70 mg/m2 free base strength) biweekly until progression. Two percutaneous core biopsies were collected from selected tumor lesions 72 hours after FMX or nal-IRI. Results: Iron particle levels were quantified by FMX-MRI in plasma, reference tissues, and tumor lesions in 13 of 15 eligible patients. On the basis of a mechanistic pharmacokinetic model, tissue permeability to FMX correlated with early FMX-MRI signals at 1 and 24 hours, while FMX tissue binding contributed at 72 hours. Higher FMX levels (ranked relative to median value of multiple evaluable lesions from 9 patients) were significantly associated with reduction in lesion size by RECIST v1.1 at early time points (P < 0.001 at 1 hour and P < 0.003 at 24 hours FMX-MRI, one-way ANOVA). No association was observed with post-FMX levels at 72 hours. Irinotecan drug levels in lesions correlated with patient's time on treatment (Spearman ρ = 0.7824; P = 0.0016). Conclusions: Correlation between FMX levels in tumor lesions and nal-IRI activity suggests that lesion permeability to FMX and subsequent tumor uptake may be a useful noninvasive and predictive biomarker for nal-IRI response in patients with solid tumors. Clin Cancer Res; 23(14); 3638–48. ©2017 AACR.
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Ramanathan et al. found a statistically significant correlation between changes in lesion size and lesion uptake of ferumoxytol in patients with metastatic solid tumors treated with Onivyde.
“They found a statistically significant correlation between changes in lesion size and lesion uptake of ferumoxytol (Figure 8D).”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [236]
Ferumoxytol uptake may serve as a suitable imaging biomarker for monitoring EPR effect and predicting nanotherapy treatment responses.
“This suggests that ferumoxtol uptake may serve as a suitable and clinically very useful imaging biomarker for monitoring the EPR effect and predicting nanotherapy treatment responses [236].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [236]
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- Authors
- Ramanathan, R. K., Korn, R. L., Raghunand, N., Sachdev, J. C., Newbold, R. G., Jameson, G., Fetterly, G. J., Prey, J., Klinz, S. G., Kim, J., Cain, J., Hendriks, B. S., Drummond, D. C., Bayever, E., & Fitzgerald, J. B.
- Affiliations
- Translational Genomics Research Institute (US)
- HonorHealth (US)
- Moffitt Cancer Center (US)
- Roswell Park Comprehensive Cancer Center (US)
- Merrimack Pharmaceuticals (United States) (US)
- Corresponding author
- Ramanathan, Ramesh K.
- Klinz, Stephan G.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2017-07-13
- Volume
- 23
- Issue
- 14
- Pages
- 3638-3648
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2584534704
- Cited by
- 183
- References
- 5
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 15 · 2023: 21 · 2022: 22 · 2021: 17 · 2020: 32 · 2019: 29 · 2018: 23 · 2017: 4
- FWCI
- 8.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NCI (P30CA016056)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › MRI in cancer diagnosis
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Keywords
- ferumoxytol, iron nanoparticles, magnetic resonance imaging, nanoliposomal irinotecan, predictive biomarkers, drug response prediction, advanced solid tumors, pharmacokinetic modeling
- MeSH terms
- Irinotecan, Adult, Aged, Aged, 80 and over, Camptothecin, Female, Humans, Liposomes, Magnetic Resonance Imaging, Male, Middle Aged, Neoplasms, Pilot Projects, Disease-Free Survival, Ferrosoferric Oxide, Nanoparticles
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