Enhanced primary tumor delineation in pancreatic adenocarcinoma using ultrasmall super paramagnetic iron oxide nanoparticle-ferumoxytol: an initial experience with histopathologic correlation

Abstract

Purpose To evaluate the role of ferumoxytol-enhanced magnetic resonance imaging (MRI) in delineating primary pancreatic tumors in patients undergoing preoperative neoadjuvant therapy. Materials and methods Eight patients with pancreatic adenocarcinoma were enrolled in this study, and underwent MRI scans at baseline, immediate post, and at the 48 hour time point after ferumoxytol injection with quantitative T2* sequences. The patients were categorized into two groups; group A received preoperative neoadjuvant therapy and group B did not. The T2* of the primary pancreatic tumor and adjacent parenchyma was recorded at baseline and the 48 hour time point. After surgery, the primary tumors were assessed histopathologically for fibrosis and inflammation. Results The mean T2* of the primary tumor and adjacent parenchyma at 48 hours in group A were 22.11 ms and 16.34 ms, respectively; in group B, these values were 23.96 ms and 23.26 ms, respectively. The T2* difference between the tumor and adjacent parenchyma in group A was more pronounced compared to in group B. The tumor margins were subjectively more distinct in group A compared to group B. Histopathologic evaluation showed a rim of dense fibrosis with atrophic acini at the periphery of the lesion in group A. Conversely, intact tumor cells/glands were present at the periphery of the tumor in group B. Conclusion Ferumoxytol-enhanced MRI scans in patients receiving preoperative neoadjuvant therapy may offer enhanced primary tumor delineation, contributing towards achieving disease-free margin at the time of surgery, and thus improving the prognosis of pancreatic carcinomas.

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study

“…Nanoliposomal carriers may thus exhibit comparably faster drug release rates than therapeutic nanoparticles with a more erosive, slower release mechanism (27,43), which could possibly explain the lack of correlation between lesion response to nal-IRI and late binding events of FMX in this study. R2 and R2 Ã mapping are accepted clinical tools for evaluating tissue iron concentrations, both for iron overload disorders (44,45) and for tracking of ultrasmall superparamagnetic iron oxide particles (18,24,46). To enable accurate lesion FMX assessments, baseline MRI signals were subtracted from later time points, and FMX phantom reference was used with all scans.…”

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging

“…The delayed uptake of magnetic nanoparticles by macrophages (73) has also been a focus of MRI for multiple applications in the pancreas as well, including improved delineation of pancreatic adenocarcinoma (17) and for quantifying inflammation in patients with early onset type I diabetes (Figure 11) (74, 75). …”

“…Signal decrease on T2/T2*- weighted images may represent high local iron concentration and/or intracellular uptake, which has many useful applications outside of the central nervous system (CNS). Indeed, intracellular uptake of ferumoxytol in abdominal organs, lymph nodes and vascular walls can be used to effectively delineate pathology in these areas (16, 17). …”

Nanomedicines for renal disease: current status and future applications

“…Silica NPs in combination with gold are being tested in thermal ablation therapy of head and neck cancers 81 . Two MRI contrast agent iron-oxide NPs (Ferumoxtran-10 ® and Ferumoxytol ® ) are in clinical trials for cancer imaging 82,83 . A therapeutic version of iron oxide NPs termed NanoTherm ® was approved in Europe in 2010 for the thermal ablation of glioblastomas (magnetic hyperthermia treatment) 84 .…”