Annexin V-CLIO: A Nanoparticle for Detecting Apoptosis by MRI

被引:146
作者
Schellenberger, Eyk A. [1 ]
Bogdanov, Alexei, Jr. [1 ]
Hoegemann, Dagmar [1 ]
Tait, Jonathan [2 ]
Weissleder, Ralph [1 ]
Josephson, Lee [1 ]
机构
[1] Massachusetts Gen Hosp, Charlestown, MA 02129 USA
[2] Univ Washington, Seattle, WA 98195 USA
关键词
Annexin V; iron oxide; MRI; apoptosis; phosphatidylserine;
D O I
10.1162/153535002320162769
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Annexin V, which recognizes the phosphatidylserine of apoptotic cells, was conjugated to crosslinked iron oxide (CLIO) nanoparticles, a functionalized superparamagnetic preparation developed for target-specific magnetic resonance imaging (MRI). The resulting nanoparticle had an average of 2.7 annexin V proteins linked per CLIO nanoparticle through disulfide bonds. Using camptothecin to induce apoptosis, a mixture of Jurkat T cells (69% healthy and 31% apoptotic) was incubated with annexin V-CLIO and was applied to magnetic columns. The result was an almost complete removal of the apoptotic cells (>99%). In a phantom MRI experiment, untreated control cells (12% apoptotic cells, 88% healthy cells) and camptothecin-treated cells (65% apoptotic cells, 35% healthy cells) were incubated with either annexin V-CLIO (1.0, 0.5, and 0.1 mu g Fe/mL) or with unlabeled CLIO. A significant signal decrease of camptothecin-treated cells relative to untreated cells was observed even at the lowest concentration tested. Unmodified CLIO failed to cause a significant signal change of apoptotic cells. Hence, annexin V-CLIO allowed the identification of cell suspensions containing apoptotic cells by MRI even at very low concentrations of magnetic substrate. Conjugation of annexin V to CLIO affords a strategy for the development of a MRI imaging probe for detecting apoptosis.
引用
收藏
页码:102 / 107
页数:6
相关论文
共 27 条
[1]  
Blankenberg FG, 2001, J NUCL MED, V42, P309
[2]   Will imaging of apoptosis play a role in clinical care? A tale of mice and men [J].
Blankenberg, FG ;
Strauss, HW .
APOPTOSIS, 2001, 6 (1-2) :117-123
[3]   In vivo detection and imaging of phosphatidylserine expression during programmed cell death [J].
Blankenberg, FG ;
Katsikis, PD ;
Tait, JF ;
Davis, RE ;
Naumovski, L ;
Ohtsuki, K ;
Kopiwoda, S ;
Abrams, MJ ;
Darkes, M ;
Robbins, RC ;
Maecker, HT ;
Strauss, HW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (11) :6349-6354
[4]   Apoptotic cell death: its implications for imaging in the next millennium [J].
Blankenberg, FG ;
Tait, JF ;
Strauss, HW .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE, 2000, 27 (03) :359-367
[5]   INTEGRIN ALPHA(V)BETA(3) ANTAGONISTS PROMOTE TUMOR-REGRESSION BY INDUCING APOPTOSIS OF ANGIOGENIC BLOOD-VESSELS [J].
BROOKS, PC ;
MONTGOMERY, AMP ;
ROSENFELD, M ;
REISFELD, RA ;
HU, TH ;
KLIER, G ;
CHERESH, DA .
CELL, 1994, 79 (07) :1157-1164
[6]   99mTc annexin V imaging of neonatal hypoxic brain injury [J].
D'Arceuil, H ;
Rhine, W ;
de Crespigny, A ;
Yenari, M ;
Tait, JF ;
Strauss, WH ;
Engelhorn, T ;
Kastrup, A ;
Moseley, M ;
Blankenberg, FG .
STROKE, 2000, 31 (11) :2692-2699
[7]   HUMAN PLACENTAL ANTICOAGULANT PROTEIN - ISOLATION AND CHARACTERIZATION [J].
FUNAKOSHI, T ;
HEIMARK, RL ;
HENDRICKSON, LE ;
MCMULLEN, BA ;
FUJIKAWA, K .
BIOCHEMISTRY, 1987, 26 (17) :5572-5578
[8]   Visualisation of cell death in vivo in patients with acute myocardial infarction [J].
Hofstra, L ;
Liem, IH ;
Dumont, EA ;
Boersma, HH ;
van Heerde, WL ;
Doevendans, PA ;
DeMuinck, E ;
Wellens, HJJ ;
Kemerink, GJ ;
Reutelingsperger, CPM ;
Heidendal, GA .
LANCET, 2000, 356 (9225) :209-212
[9]   High throughput magnetic resonance imaging for evaluating targeted nanoparticle probes [J].
Högemann, D ;
Ntziachristos, V ;
Josephson, L ;
Weissleder, R .
BIOCONJUGATE CHEMISTRY, 2002, 13 (01) :116-121
[10]   Improvement of MRI probes to allow efficient detection of gene expression [J].
Högemann, D ;
Josephson, L ;
Weissleder, R ;
Basilion, JP .
BIOCONJUGATE CHEMISTRY, 2000, 11 (06) :941-946