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Moving Toward Multicenter Therapeutic Trials in Amyotrophic Lateral Sclerosis: Feasibility of Data Pooling Using Different Translocator Protein PET Radioligands

Authors
  • Van Weehaeghe, Donatienne; 110770;
  • Babu, Suma;
  • De Vocht, Joke; 74599;
  • Zurcher, Nicole R;
  • Chew, Sheena;
  • Tseng, Chieh-En J;
  • Loggia, Marco L;
  • Koole, Michel; 54596;
  • Rezaei, Ahmadreza; 76231;
  • Schramm, Georg; 102742;
  • Van Damme, Philip; 34370;
  • Hooker, Jacob M;
  • Van Laere, Koen; 40740;
  • Atassi, Nazem;
Publication Date
Nov 01, 2020
Source
Lirias
Keywords
Language
English
License
Unknown
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Abstract

Neuroinflammation has been implicated in amyotrophic lateral sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, TSPO radioligands have some challenges to overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (11C-PBR28 and 18F-DPA714) is feasible, after validation of an established 11C-PBR28 PET pseudo reference analysis technique for 18F-DPA714. Methods: Seven ALS patients from Belgium (58.9 ± 6.7 y old, 5 men and 2 women), 8 healthy volunteers from Belgium (52.1 ± 15.2 y old, 3 men and 5 women), 7 ALS patients from the United States (53.4 ± 9.8 y old, 5 men and 2 women), and 7 healthy volunteers from the United States (54.6 ± 9.6 y old, 4 men and 3 women) from a previously published study underwent dynamic 18F-DPA714 (Leuven, Belgium) or 11C-PBR28 (Boston, Massachusetts) PET/MRI. For 18F-DPA714, maps of total volume of distribution (VT) were compared with SUV ratio (SUVR) images from 40 to 60 min after injection (SUVR40-60) calculated using the pseudo reference regions cerebellum, occipital cortex, and whole brain (WB) without ventricles. For 11C-PBR28, SUVR images from 60 to 90 min after injection using the WB without ventricles were calculated. Results: In line with previous studies, increased 18F-DPA714 uptake (17.0% ± 5.6%) in primary motor cortices was observed in ALS subjects, as measured by both VT and SUVR40-60 approaches. The highest sensitivity was found for SUVR calculated using the WB without ventricles (average cluster, 21.6% ± 0.1%). 18F-DPA714 VT ratio was highly correlated with the SUVR40-60 (r > 0.8, P < 0.001). A similar pattern of increased uptake (average cluster, 20.5% ± 0.5%) in the primary motor cortices was observed in ALS subjects for 11C-PBR28 SUVR calculated using the WB without ventricles. Analysis of the 18F-DPA714 and 11C-PBR28 data together resulted in a more extensive pattern of significantly increased glial activation bilaterally in the primary motor cortices. Conclusion: The same pseudo reference region analysis technique for 11C-PBR28 PET can be extended toward 18F-DPA714 PET. Therefore, in ALS, standardized analysis across these 2 tracers enables pooling of TSPO PET data across multiple centers and increases the power of TSPO as a biomarker for future therapeutic trials. / status: published

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