Optimized Quantification of Translocator Protein Radioligand ¹⁸F-DPA-714 Uptake in the Brain of Genotyped Healthy Volunteers

Abstract

Translocator protein (TSPO) is expressed at a low level in healthy brain and is upregulated during inflammatory processes that may occur in neurodegenerative diseases. Thus, TSPO may be a suitable in vivo indicator of neurodegeneration. Here, we quantified the 18 F-DPA-714 radioligand in healthy TSPO-genotyped volunteers and developed a method to eliminate the need for invasive arterial blood sampling. Methods: Ten controls (7 high-affinity binders [HABs] and 3 mixed-affinity binders [MABs]) underwent 18 F-DPA-714 PET with arterial and venous sampling. 18 F-DPA-714 binding was quantified with a metabolite-corrected arterial plasma input function, using the 1-and 2-tissue-compartment models (TCMs) as well as the Logan analysis to estimate total volume distribution (V T ) in the regions of interest. Alternative quantification methods were tested, including tissue-to-plasma ratio or population-based input function approaches normalized by late time points of arterial or venous samples. Results: The distribution pattern of 18 F-DPA-714 was consistent with the known distribution of TSPO in humans, with the thalamus displaying the highest binding and the cerebellum the lowest. The 2-TCM best described the regional kinetics of 18 F-DPA-714 in the brain, with good identifiability (percentage coefficient of variation , 5%). For each region of interest, V T was 47.6% ± 6.3% higher in HABs than in MABs, and estimates from the 2-TCM and the Logan analyses were highly correlated. Equilibrium was reached at 60 min after injection. V T calculated with alternative methods using arterial samples was strongly and significantly correlated with that calculated by the 2-TCM. Replacement of arterial with venous sampling in these methods led to a significant but lower correlation. Conclusion: Genotyping of subjects is a prerequisite for a reliable quantification of 18 F-DPA-714 PET images. The 2-TCM and the Logan analyses are accurate methods to estimate 18 F-DPA-714 V T in the human brain of both HAB and MAB individuals. Population-based input function and tissue-to-plasma ratio with a single arterial sample are promising alternatives to classic arterial plasma input function. Substitution with venous samples is promising but still requires methodologic improvements.

The impact of the rs6971 polymorphism in TSPO for quantification and study design

“…Using 18 F-PBR111 we showed these rank order differences in V T values in all regions of interest [12]. Similar results were reported for V T values obtained with 18 F-FEPPA [13] and 18 F-DPA-714 [14], and both standardized uptake values (SUV) [15] and V T values [16] obtained with 11 C-PBR28. Using the affinity ratio derived from in vitro studies (R = K d-LAB /K d-HAB , which assumes the HAB and LAB affinities are the same in MABs), it is also possible to estimate the ratio of the binding potential (BP ND ) between the three groups.…”

Sifting through the surfeit of neuroinflammation tracers

“…Supervised cluster analysis of [ 18 F]DPA-714 uptake in healthy human brain shown the preponderance of reference voxels to be within the cerebellum; the forebrain BP ND was the range of 0.2-0.6, with little effect of TSPO allele. 106 This magnitude of BP ND is low compared to other reports with [ 11 C]DPA-713 and [ 18 F]DPA-714 ( Table 1), suggesting that the reference cluster indeed underestimates the specific binding.…”

Imaging the neuroimmune response to alcohol exposure in adolescent baboons: a TSPO PET study using 18F‐DPA‐714

“…Several TSPO radioligands, including 18 F‐DPA‐714, have reached the clinical status and are currently used to investigate the neuroimmune component of various patho‐physiological states of the CNS in human (Lavisse et al . ; Hamelin et al . ).…”