Ultra‐small superparamagnetic iron oxides for metastatic lymph node detection: back on the block

• Published in: Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology Vol. 10; no. 1
• Main Authors: Fortuin, Ansje S., Brüggemann, Roger, Linden, Janine, Panfilov, Ilia, Israël, Bas, Scheenen, Tom W.J., Barentsz, Jelle O.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.01.2018
• ISSN: 1939-5116; 1939-0041
• DOI: 10.1002/wnan.1471

In the past 15 years, encouraging clinical results for the detection of small lymph node metastases was obtained by the use of Combidex‐enhanced MRI (CEM, also known as magnetic resonance lymphography). Withdrawal of the European Medicines Agency approval application by the manufacturer made it impossible for patients to benefit from this agent; a loss, especially for men with prostate cancer. Current conventional imaging techniques are not as accurate as CEM is, thus a surgical diagnostic exploration (extended lymph node dissection) is still the preferred technique to evaluate the lymph nodes, resulting in peri‐ and postoperative complications. In 2013, the Radboud University Medical Center (Radboudumc) obtained all licenses and documentation for the production process of Combidex (ferumoxtran‐10), and manufactured the contrast agent under supervision of the Department of Pharmacy. Since 2014, 310 men with prostate cancer have been examined with CEM in the Radboudumc. Within this cohort, seven minor possibly contrast‐related adverse effects were observed after administration of Combidex. As the contrast agent is now back again in the Netherlands, this review highlights the working mechanism, previous results, observed side effects since the reintroduction, and the future perspectives for Combidex. WIREs Nanomed Nanobiotechnol 2018, 10:e1471. doi: 10.1002/wnan.1471 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Combidex‐enhanced magnetic resonance imaging (MRI) at 3 T of a 53‐year‐old patient with recurrent prostate cancer after radical prostatectomy and radiotherapy (PSA‐level 3.9 ng/mL). Twenty‐seven hours after administration of Combidex benign lymph nodes have accumulated the contrast agent, becoming black on a three‐dimensional (3D) iron‐sensitive MRI scan. Metastatic lymph nodes retain signal and therefore stay white. A large (7 mm) metastatic lymph node is visible on Combidex‐enhanced MRI as a white spherical structure in two orthogonal planes through the node [blue circles in coronal (a) and axial images (b)]. A smaller metastatic white node (2–3 mm) is indicated with red circles in the coronal (c) and axial (d) reconstructions (orthogonal planes through the node of interest) of the 3D data set. The other small spherical structures are blood vessels, best appreciated when scrolling through the 3D image data set.