11C-NMSP/ 18F-FDG microPET to monitor neural stem cell transplantation in a rat model of traumatic brain injury.
OBJECTIVE
To investigate whether (11)C-N-methylspiperone ((11)C-NMSP) microPET could be used for imaging neural stem cells (NSCs) transplantation in a rat model of traumatic brain injury.


METHODS
NSCs were induced to express dopamine receptor type 2 (DRD(2)), then confirmed by RT-PCR, Western blotting and immunocytochemistry. Eighteen rats were subjected to focal traumatic brain injury in the right parietal lobe and then assigned randomly to the transplantation group and the control group. NSCs labeled with 5-bromo-2-deoxyuridine (BrdU) were transplanted into the cerebral lesion of the transplantation group. MicroPET scan using (11)C-NMSP and (18)F-FDG were performed to detect the DRD(2) expression of transplanted NSCs and the regional glucose metabolism in the cerebral lesion, respectively. Behavioral neurological function of rats were also tested.


RESULTS
Histological analysis identified viable NSCs. Western blotting and immunofluorescence showed high level of NSCs-induced DRD(2) expression. Immunostaining demonstrated high levels of survived BrdU+ and DRD(2)+ donor cells in the cerebral lesion 2 weeks after transplantation. The lesion-to-normal contralateral ratio (L/N ratio) of (11)C-NMSP in the cerebral lesion decreased significantly from 97% to 68% after injury and increased dramatically to 137% 1 day after the transplantation and then decreased gradually. Glucose metabolism showed a decrease of 35% in the cerebral lesion 1 day after injury and recovered to 87% 2 weeks after transplantation. The behavioral neurological function of the transplantation group was significantly improved compared with the control group.


CONCLUSIONS
This study verified that (11)C-NMSP microPET can be used to assess the NSCs-induced DRD(2) expression in rat model.
Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, China.
Hong
H
Zhang
Xuesheng
X
Zheng
Xiaofeng
X
Yang
Shengwei
S
Fang
Gang
G
Shen
Chunlei
C
Zhao
Mei
M
Tian
D000818:Animals; D001930:Brain Injuries / Q000601:surgery*; D002250:Carbon Radioisotopes; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D009474:Neurons / Q000166:cytology* / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics; D013134:Spiperone / Q000031:analogs & derivatives*; D033581:Stem Cell Transplantation
D002250:Carbon Radioisotopes; D017448:Receptors, Dopamine D2; D019788:Fluorodeoxyglucose F18; D013134:Spiperone; C039167:3-N-methylspiperone