Optimized quantification of translocator protein radioligand $^{18}$F-DPA-714 uptake in the brain of genotyped healthy volunteers

Sonia Lavisse (1) , Daniel Garcia-Lorenzo (2) , Marie-Anne Peyronneau (3, 4) , Benedetta Bodini (2) , Claire Thiriez (5, 6) , Bertrand Kuhnast (4, 3) , Claude Comtat (3, 4) , Philippe Remy (1, 6, 5) , Bruno Stankoff (2, 7) , Michel Bottlaender (3, 4)

1 LMN - Laboratoire des Maladies Neurodégénératives - UMR 9199
2 ICM - Institut du Cerveau = Paris Brain Institute
3 SHFJ - Service Hospitalier Frédéric Joliot
4 IMIV - U1023 - ERL9218 - Imagerie Moléculaire in Vivo
5 CIC Henri Mondor - Centre d'Investigation Clinique Henri Mondor
6 Service de neurologie [Mondor]
7 Hôpital Lariboisière

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.

Mots clés: genotyped human; TSPO; quantification; PET; $^{18}$F-DPA-714

Domaines: Neurobiologie

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⟩