Optimized quantification of translocator protein radioligand $^{18}$F-DPA-714 uptake in the brain of genotyped healthy volunteers - CEA - Commissariat à l’énergie atomique et aux énergies alternatives Access content directly
Journal Articles Journal of Nuclear Medicine Year : 2015

Optimized quantification of translocator protein radioligand $^{18}$F-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: Gen-otyping 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.

Domains

Neurobiology
Fichier principal
Vignette du fichier
Lavisse-JNM2015.pdf (885.92 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

cea-02132948 , version 1 (17-05-2019)

Identifiers

Cite

Sonia Lavisse, Daniel Garcia-Lorenzo, Marie-Anne Peyronneau, Benedetta Bodini, Claire Thiriez, et al.. Optimized quantification of translocator protein radioligand $^{18}$F-DPA-714 uptake in the brain of genotyped healthy volunteers. Journal of Nuclear Medicine, 2015, 56 (7), pp.1048-1054. ⟨10.2967/jnumed.115.156083⟩. ⟨cea-02132948⟩
81 View
207 Download

Altmetric

Share

Gmail Facebook X LinkedIn More