Preclinical evaluation of TSPO ligand [18F]DPA-714 for PET imaging of glioma

Objectives Translocator protein (TSPO) is a crucial trans-mitochondrial membrane protein involved in numerous cellular functions that include cholesterol metabolism, steroidogenesis, and apoptosis. Elevated TSPO expression is found in numerous diseases, ranging from neuroinflammation to cancer. We recently reported successful use of the aryloxyanilide [18F]PBR06 for preclinical imaging of glioma. Building upon these studies, we have evaluated the high-affinity pyrazolopyrimidine-based TSPO ligand, [18F]DPA-714, to quantitatively assess TSPO expression in a preclinical model of glioma.

Methods [18F]DPA-714 was synthesized in high specific activity using published methods. Wistar rats were stereotactically inoculated in the right hemisphere with tumor cells (C6 glioma) or vehicle. Rats were imaged in a microPET system. A 90 min dynamic acquisition was started simultaneously with injection of [18F]DPA-714. Arterial blood was collected to derive the arterial input function (AIF) and HPLC radiometabolite analysis performed on select blood samples. Compartmental modeling of the PET data was performed using a corrected AIF and PMOD program.

Results [18F]DPA-714 preferentially accumulated in tumor with little uptake in healthy brain, facilitating excellent contrast between tumor and normal tissue. Time-activity curves from tumor and healthy brain regions could be fit to a 3-compartment, 4-parameter model. Infusion with cold ligand displaced tracer binding approximately 90%. Accumulation of [18F]DPA-714 in tumor and adjacent brain agreed with ex vivo assay of TSPO protein levels by Western blot and quantitative IHC.

Conclusions These data illustrate [18F]DPA-714 as a promising tracer for visualization of TSPO-expressing tumors, with uptake accurately reflecting TSPO densities in normal brain and tumor tissue. Accordingly, [18F]DPA-714 appears to be an ideal candidate probe for exploration of TSPO expression in other preclinical cancer models with future applications in human cancer imaging studies