PET Imaging of Vesicular Monoamine Transporter 2 in Early Diabetic Retinopathy Using [ 18 F]FP-(+)-DTBZ
- PDF / 1,770,148 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 90 Downloads / 179 Views
RESEARCH ARTICLE
PET Imaging of Vesicular Monoamine Transporter 2 in Early Diabetic Retinopathy Using [18F]FP-(+)-DTBZ Jun Li,1,2 Ping Chen,1 Yong Bao,3 Yu Sun,1 Jiang He,2 Xingdang Liu1 1
Department of Nuclear Medicine, Huashan Hospital, Fudan University, No. 12 Urumchi Middle Road, Jing’an District, Shanghai, 200040, China 2 Department of Radiology and Medical imaging, University of Virginia, Charlottesville, VA, 22908, USA 3 Department of Pharmacology and Biochemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China
Abstract Purpose: Diabetic retinopathy (DR) is characterized by dopaminergic neuron loss in the retina of the eyes. [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) positron emission tomography (PET) has been shown to detect dopaminergic neuron loss. The study is to investigate the feasibility of PET imaging with [18F]FP-(+)-DTBZ for early diagnosis of diabetic retinopathy (DR) in diabetes mellitus (DM) rat models. Methods: The DM rat model was established by a single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg). After 4 weeks, 8 weeks, and 12 weeks of STZ injection, the retinas of the rats were evaluated by electroretinogram (ERG), color fundus photography (CFP), fundus fluorescein angiography (FFA), and small animal PET scan with [18F]FP-(+)-DTBZ by targeting vesicular monoamine transporter 2 (VMAT2). [18F]FP-(+)-DTBZ uptake in retina was quantified as standardized uptake value (SUV). Immunofluorescence staining and Western blot were also performed to confirm the expression level of VMAT2 in retina. Results: ERG dysfunction was observed at 8 weeks in STZ-diabetic rats, evidenced by smaller amplitudes of oscillatory potentials (OPs) when compared with OPs in normal rats. CFP and FFA showed no significant difference in vascular leakage and neovascularization between STZdiabetic retinas and normal ones until 8 weeks. PET imaging revealed that the SUV of [18F]FP(+)-DTBZ was significantly lower in the STZ-diabetic retinas compared with the normal ones as early as of week 4. The results from immunofluorescence staining and Western blots confirmed the early findings in PET imaging studies. Conclusions: Early DR can be non-invasively detected with PET imaging using [18F]FP-(+)DTBZ targeting VMAT2. The expression level of VMAT2 in retina may act as a new biomarker for early DR diagnosis. Key words: Vesicular monoamine transporter 2, Diabetic retinopathy, PET, [18F]FP-(+)-DTBZ
Introduction Correspondence to: Xingdang Liu; e-mail: [email protected]
Diabetic retinopathy (DR), the main microvascular complication of diabetes mellitus (DM), is the leading cause of vision impairment and loss among DM patients [1, 2]. It
Li J. et al.: PET imaging of vesicular monoamine transporter 2
ultimately affects more than 90 % of diabetic patients to some degree. The appearance and the severity of the symptoms correlate with the duration of diabetes. Approximately 10 % of patients whose diabetic duration is more than 15 years develop severe visual impairment and even blin
Data Loading...
