RT Journal Article
T1 A novel molecular magnetic resonance imaging agent targeting activated leukocyte cell adhesion molecule as demonstrated in mouse brain metastasis models.
A1 Zarghami, Niloufar
A1 Soto, Manuel Sarmiento
A1 Perez-Balderas, Francisco
A1 Khrapitchev, Alexandre A
A1 Karali, Christina Simoglou
A1 Johanssen, Vanessa A
A1 Ansorge, Olaf
A1 Larkin, James R
A1 Sibson, Nicola R
K1 CD166)
K1 Magnetic resonance imaging
K1 activated leukocyte cell adhesion molecule (ALCAM
K1 brain metastasis
K1 inflammation
K1 molecular imaging
AB Molecular magnetic resonance imaging (MRI) allows visualization of biological processes at the molecular level. Upregulation of endothelial ALCAM (activated leukocyte cell adhesion molecule) is a key element for leukocyte recruitment in neurological disease. The aim of this study, therefore, was to develop a novel molecular MRI contrast agent, by conjugating anti-ALCAM antibodies to microparticles of iron oxide (MPIO), for detection of endothelial ALCAM expression in vivo. Binding specificity of ALCAM-MPIO was demonstrated in vitro under static and flow conditions. Subsequently, in a proof-of-concept study, mouse models of brain metastasis were induced by intracardial injection of brain-tropic human breast carcinoma, lung adenocarcinoma or melanoma cells to upregulate endothelial ALCAM. At selected time-points, mice were injected intravenously with ALCAM-MPIO, and ALCAM-MPIO induced hypointensities were observed on T2*-weighted images in all three models. Post-gadolinium MRI confirmed an intact blood-brain barrier, indicating endoluminal binding. Correlation between endothelial ALCAM expression and ALCAM-MPIO binding was confirmed histologically. Statistical analysis indicated high sensitivity (80-90%) and specificity (79-83%) for detection of endothelial ALCAM in vivo with ALCAM-MPIO. Given reports of endothelial ALCAM upregulation in numerous neurological diseases, this advance in our ability to image ALCAM in vivo may yield substantial improvements for both diagnosis and targeted therapy.
YR 2020
FD 2020-11-05
LK https://hdl.handle.net/10668/26554
UL https://hdl.handle.net/10668/26554
LA en
DS RISalud
RD Apr 10, 2025