The Place of PET to Assess New Therapeutic Effectiveness in Neurodegenerative Diseases

Table 3

Neuroinflammation imaging approach to assess therapeutic effectiveness.

Disorder	Physiopathological approach	Radioligand	Population	Therapeutical class	Main findings	References
AD	Neuroinflammation TSPO	^18F-GE180	Preclinical: transgenic APdE9 mice were treated with JZL184 () or with vehicle ()	Monoacylglycerol lipase inhibitor: JZL184 40 mg/kg/d	In JZL184-treated mice, there was a very slight decreasing trend in tracer uptake in multiple brains areas compared to vehicle-treated APdE9 mice.	Pihlaja et al. [56]
MS	Neuroinflammation TSPO	^18F-GE180	Preclinical: chronic focal EAE-like lesions were induced in rats via stereotactic intrastriatal injection of BCG and subsequent activation using an intradermal injection of BCG	Selective immunosuppressant (S1P receptor antagonist): fingolimod 0.3 mg/kg/d	Treatment with fingolimod for 28 days resulted in a clear reduction in the binding of trace when compared with vehicle-treated animals.	Airas et al. [52]
			Animals were then treated for 28 days with either fingolimod () or vehicle ()		Quantification of the binding of the radiotracer revealed a significant reduction in the BPND of ^18F-GE180 after treatment with fingolimod.
	Neuroinflammation TSPO	^11C-PK11195	Clinical: 9 drug-naïve RRMS patients were scanned at baseline before initiating GA and again after 1 year of GA treatment	Immunomodulatory: GA 20 mg/d	Significantly decreased tracer BPND per unit volume 3.17% in whole brain between baseline and 1 year and especially in supratentorial brain, infratentorial brain, cerebral white matter, cortical grey matter, thalamus and putamen.	Ratchord et al. [51]
	Neuroinflammation TSPO	^18F-FEDAA1106	Clinical: RRMS patients in acute relapse: 6 drug-naïve patients and 3 patients on interferon beta therapy versus 5 HC	Immunomodulatory: interferon beta	No significant difference of tracer BPND or VT between the three groups: MS without treatment, MS with interferon beta therapy, and normal control.	Takano et al. [50]
	Neuroinflammation TSPO	^11C-PK11195	Clinical: 10 RRMS patients were scanned at baseline before initiating fingolimod and again after 6 months of treatment	Selective immunosuppressant (S1P receptor antagonist): fingolimod	Tracer binding was reduced (−12.3%) in the T2 lesion area after 6 months of fingolimod treatment, but not in the areas of NAWM or grey matter.	Sucksdorff et al. [53]
			7 patients were scanned 2 months following the treatment initiation		5/7 patients showed a slight increase tracer DVR in NAWM during the first 2 months of fingolimod treatment.
					6/7 patients showed a slight increase in cortical gray matter after 2 months.
MSA	Neuroinflammation TSPO	^11C-PK11195	Clinical: 8 MSA-P patients: 3 with minocycline versus 5 in placebo arm	Tetracycline with anti-inflammatory effects: minocycline 200 mg/d	Compared to baseline, tracer BPND decreased in caudate nucleus, thalamus, midbrain and cerebellum for 2/3 treated patients after 24 weeks of minocycline.	Dodel et al. [54]
			Two groups were followed up for 6 months		In placebo group, tracer BPND is increased in most regions after 6 months.
PD	Neuroinflammation TSPO	^11C-PK11195	Clinical: 5 PD patients were scanned before and after one month of celecoxib	COX-2 inhibitor: celecoxib 100 mg/d	Tracer binding potential and distribution volume after celecoxib treatment were slightly higher.	Bartels et al. [55]
	Neuroinflammation TSPO	^11C-PBR28	Clinical: 24 PD patients: 18 with AZD3241 versus 6 in placebo arm	Myeloperoxidase inhibitor: AZD3241 600 mg/12 h	There was no significant difference in changes of VT between the treatment groups.	Jucaite et al. [57]
			16 PD patients in AZD3241 arm were followed-up for 8 weeks		AZD3241 significantly reduced VT in regions of the nigrostriatal pathway compared to baseline VT values at 4 weeks and at 8 weeks.

AD, Alzheimer’s disease; BCG, bacillus Calmette-Guérin; BP_ND, binding potential; DVR, distribution volume ratio; EAE, experimental autoimmune encephalitis; GA, glatiramer acetate; MS, multiple sclerosis; MSA, multiple system atrophy, NAWM, normal appearing white matter; PD, Parkinson’s disease; RRMS, relapsing-remitting multiple sclerosis; S1P, sphingosine 1-phosphate; V_T, total distribution volume.