Open AccessEvaluation of the novel USPIO GEH121333 for MR imaging of cancer immune responses
Author(s) -
Shi Qiaoyun,
Pisani Laura J.,
Lee Yauk K.,
Messing Solomon,
Ansari Celina,
Bhaumik Srabani,
Lowery Lisa,
Lee Brian D.,
Meyer Dan E.,
DaldrupLink Heike E.
Publication year - 2013
Publication title -
contrast media & molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.714
H-Index - 50
eISSN - 1555-4317
pISSN - 1555-4309
DOI - 10.1002/cmmi.1526
Subject(s) - ferumoxytol , medicine , histopathology , relaxometry , pathology , immune system , magnetic resonance imaging , immunology , radiology , spin echo
Tumor‐associated macrophages (TAM) maintain a chronic inflammation in cancers, which is associated with tumor aggressiveness and poor prognosis. The purpose of this study was to: (1) evaluate the pharmacokinetics and tolerability of the novel ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) compound GEH121333; (2) assess whether GEH121333 can serve as a MR imaging biomarker for TAM; and (3) compare tumor MR enhancement profiles between GEH121333 and ferumoxytol. Blood half‐lives of GEH121333 and ferumoxytol were measured by relaxometry ( n = 4 each). Tolerance was assessed in healthy rats injected with high dose GEH121333, vehicle or saline ( n = 4 each). Animals were monitored for 7 days regarding body weight, complete blood counts and serum chemistry, followed by histological evaluation of visceral organs. MR imaging was performed on mice harboring MMTV‐PyMT‐derived breast adenocarcinomas using a 7 T scanner before and up to 72 h post‐injection (p.i.) of GEH121333 ( n = 10) or ferumoxytol ( n = 9). Tumor R 1 , R 2 * relaxation rates were compared between different experimental groups and time points, using a linear mixed effects model with a random effect for each animal. MR data were correlated with histopathology. GEH121333 showed a longer circulation half‐life than ferumoxytol. Intravenous GEH121333 did not produce significant adverse effects in rats. All tumors demonstrated significant enhancement on T 1 , T 2 and T 2 *‐weighted images at 1, 24, 48 and 72 h p.i. GEH121333 generated stronger tumor T 2 * enhancement than ferumoxytol. Histological analysis verified intracellular compartmentalization of GEH121333 by TAM at 24, 48 and 72 h p.i. MR imaging with GEH121333 nanoparticles represents a novel biomarker for TAM assessment. This new USPIO MR contrast agent provides a longer blood half‐life and better TAM enhancement compared with the iron supplement ferumoxytol. Copyright © 2013 John Wiley & Sons, Ltd.