Inflammatory bowel disease: MR- and SPECT/CT-based macrophage imaging for monitoring and evaluating disease activity in experimental mouse model--pilot study.
OBJECTIVE
To evaluate the feasibility of using magnetic resonance (MR) imaging and single photon emission computed tomography (SPECT)/computed tomography (CT) to visualize the in vivo recruitment of iron oxide-labeled macrophages and indium 111 ((111)In)-labeled macrophages in inflammatory bowel disease (IBD) and to monitor disease activity.


METHODS
This study had institutional animal care and use committee approval. Twenty-seven C57/B6 mice with dextran sodium sulfate (DSS)-induced IBD and control mice were included. Peritoneal macrophages were harvested from seven thioglycollate-treated mice and were labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Macrophage iron content was determined by using inductively coupled plasma mass spectrometry. SPIO nanoparticle-labeled macrophages (5 × 10(6)) were intravenously administered. Mice with DSS-induced IBD (n = 8) and control mice (n = 6) were imaged with a 9.4-T MR imaging unit at 0, 5, and 24 hours after macrophage administration. Percentage normalized enhancement (NE) was calculated for the intestinal wall and liver 24 hours after injection. Six mice with IBD coinjected with SPIO nanoparticles and (111)In oxine-labeled macrophages were imaged with MR imaging and SPECT/CT after 24 hours. The pharmacokinetics and biodistribution of the implanted macrophages were determined. Correlation between percentage NE and IBD scores was calculated.


RESULTS
Ex vivo mass spectrometry revealed strong SPIO nanoparticle uptake (7.4 pg iron per cell). R2* correlated with cell number (r = 0.9813, P < .05). Percentage NE correlated with both clinical (r = 0.924) and pathologic (r = 0.795) IBD score. Cell circulation half-life in the first and second phases was 0.32 hour and 10.2 hours, respectively. SPECT/CT showed that approximately 3% of the injected dose was present in the intestines 24 hours after injection; this was confirmed at MR imaging and histologic examination. Indium 111-labeled cells were present in all tissue associated with the reticuloendothelial system or mononuclear phagocyte system at 24 hours.


CONCLUSIONS
SPIO nanoparticles and (111)In-labeled macrophages could be observed in vivo at MR imaging and SPECT/CT in mice with IBD. Percentage NE at MR imaging correlates with disease activity.
From the Department of Radiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, 639 Zhizaoju Road, Shanghai, China 200011 (Y.W., X.T.); Department of Radiology, East Hospital, Tongji University, School of Medicine, Shanghai, China (Y.W., Z.W.); Department of Radiology (K.B., C.Y.T.), Department of Medicine, Immunology Institute (R.Z.), and Department of Pharmacology and Systems Therapeutics (C.H.), Mount Sinai School of Medicine, New York, NY; and Department of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China (J.X.).
Yingwei
Y
Wu
Karen
K
Briley-Saebo
Jingyuan
J
Xie
Ruihua
R
Zhang
Zhongqiu
Z
Wang
Cijiang
C
He
Cheuk Ying
CY
Tang
Xiaofeng
X
Tao
D000818:Animals; D003287:Contrast Media; D003911:Dextrans; D004195:Disease Models, Animal; D007205:Indium Radioisotopes; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D015636:Magnesium Chloride; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D008810:Mice, Inbred C57BL; D064847:Multimodal Imaging; D053758:Nanoparticles; D019047:Phantoms, Imaging; D010865:Pilot Projects; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
D003287:Contrast Media; D003911:Dextrans; D007205:Indium Radioisotopes; D058185:Magnetite Nanoparticles; D015636:Magnesium Chloride; C065507:ferumoxides