[18F]DPA-714: Direct Comparison with [11C]PK11195 in a Model of Cerebral Ischemia in Rats

Purpose

Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. ¹⁸F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of ¹⁸F]DPA-714, it was compared directly to ¹¹C]PK11195 in experimental cerebral ischaemia in rats.

Methods

Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with ¹¹C]PK11195 and/or ¹⁸F]DPA-714 under anaesthesia.

Results

Uptake of ¹¹C]PK11195 vs ¹⁸F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with ¹¹C]PK11195 or with ¹⁸F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of ¹¹C]PK11195 and ¹⁸F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for ¹¹C]PK11195 vs ¹⁸F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3–1.9, 95%CI) fold by linear regression) for ¹⁸F]DPA-714.

Conclusions

In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that ¹⁸F]DPA-714 displayed a higher signal-to-noise ratio than ¹¹C]PK11195. Our results suggest that, with the longer half-life of ¹⁸F] which facilitates distribution of the tracer across PET centre, ¹⁸F]DPA-714 is a good alternative for TSPO imaging.