PET Imaging of Vesicular Monoamine Transporter 2 in Early Diabetic Retinopathy Using [18F]FP-(+)-DTBZ.

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 STZ-diabetic 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.