18F-PBR06 Versus 11C-PBR28 PET for Assessing White Matter Translocator Protein Binding in Multiple Sclerosis.

Abstract

BACKGROUND AND PURPOSE:

F-PBR06 and C-PBR28 are second-generation PET radioligands targeting the 18-kd translocator protein to assess microglial activation. We directly compared F-PBR06 and C-PBR28 for detecting brain translocator protein binding in multiple sclerosis (MS).

METHODS:

Six patients with MS (4 women; mean age ± SD, 32.1 ± 4.9 [range, 23.5-37.4 years]; Expanded Disability Status Scale score 2.3 ± 1.2 [range, 1.0-4.0]) underwent brain PET with both ligands, along with 3-T MRI. MRI was coregistered to the summed 60- to 90-minute PET images. SUV ratios (SUVRs), derived by normalization to global brain radioactivity, were obtained for whole-brain white matter (WM), supratentorial WM, normal-appearing WM (NAWM), and T2 (fluid-attenuated inversion recovery) hyperintense and T1 hypointense MS WM lesions. The highest mean SUVR for the fluid-attenuated inversion-recovery lesional slices was defined as SUVRmax.

RESULTS:

F-PBR06 and C-PBR28 were moderately intercorrelated for whole-brain WM SUVR (r = 0.83, P = 0.04) and supratentorial WM SUVR (r = 0.81, P = 0.05) but not for SUVRs of NAWM, T1 lesions, T2 lesions, or SUVRmax. Both tracers demonstrated that SUVR was higher in NAWM than in T1 and T2 lesions (all P < 0.05). F-PBR06 (but not C-PBR28) demonstrated a higher SUVR in T1 versus T2 lesions (0.85 ± 0.07 vs 0.78 ± 0.03, P = 0.03). F-PBR06-derived (but not C-PBR28) SUVRmax correlated with both Expanded Disability Status Scale score (r = 0.82, P = 0.04) and timed 25-ft walking speed (r = 0.89, P = 0.01).

CONCLUSIONS:

Our preliminary results suggest an association between microglial activation and physical disability in MS. Microglial detection in lesions was not interchangeable between the tracers, with a higher clinical relevance suggested for F-PBR06.

• Authors: Tarun Singhal, Kelsey OʼConnor, Shipra Dubey, Anthony P Belanger, Shelley Hurwitz, Renxin Chu, Shahamat Tauhid, Marie F Kijewski, Marcelo F DiCarli, Howard L Weiner, Rohit Bakshi
• Journal: Clinical nuclear medicine (Clin Nucl Med) Vol. 43 Issue 9 Pg. e289-e295 (Sep 2018) ISSN: 1536-0229 [Electronic] United States
• PMID: 30004939 (Publication Type: Comparative Study, Journal Article)

Chemical References

• (methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine
• Acetanilides
• N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline
• Pyrimidines
• Radiopharmaceuticals

Topics

• Acetanilides
• Adult
• Female
• Humans
• Male
• Multiple Sclerosis (diagnostic imaging)
• Positron-Emission Tomography (methods)
• Pyrimidines
• Radiopharmaceuticals
• White Matter (diagnostic imaging)