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

Table 4

Neurotransmission imaging approach to assess therapeutic effectiveness.

Disorder	Physiopathological approach	Radioligand	Population	Therapeutical class	Main findings	References
PD	Dopamine neurotransmission	^11C-raclopride	18 previously untreated PD patients and 14 healthy volunteer subjects	Levodopa/lisuride	3 to 4 months’ oral therapy with LD or lisuride does not change striatal dopamine D2-receptor density in PD patients.	Antonini et al. [64]
	Dopamine neurotransmission	^11C-raclopride	9 patients with PD at an early drug-naive stage and 3–5 years later and 10 healthy controls in the same age range	Levodopa/lisuride	After 3–5 years, binding was significantly reduced in the putamen () and caudate nucleus () compared with baseline. These results indicate long-term downregulation of striatal dopamine D2 receptor binding in PD.	Antonini et al. [65]
	Dopamine neurotransmission	^11C-raclopride	16 advanced PD patients	Levodopa	Following LD, mean caudate and putamen ^11C-raclopride BPs were significantly lower versus baseline, consistent with increased synaptic DA.	Pavese et al. [66]
					A two-scan RAC PET study has reported, in advanced PD cases that, improvement in bradykinesia and rigidity scores following oral DA medication administration were significantly correlated with reductions in RAC binding suggesting an effect of increased DA on the striatal D2 receptors.
	Dopamine neurotransmission	^18F-6-fluorodopa	67 patients with IP, 52 with fluctuations and 15 with a stable response to LD	Levodopa	A 28% decrease in presynaptic terminal function in the putamen of PD patients with a fluctuating response to LD compared to the stable responders.	de la Fuente-Fernández et al. [68]
	Dopamine neurotransmission	^18F-6-fluorodopa	9 patients with PD followed for 10 to 72 months after human embryonic mesencephalic tissue	Human embryonic mesencephalic tissue	^18F-6-DOPA uptake increases in the striatum following the transplantation.	Wenning et al. [67]
	Dopamine neurotransmission	^18F-6-fluorodopa	40 patients with PD	Transplantation of human embryonic dopamine neurons	Among younger patients (60 years old or younger), standardized tests of PD revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication.	Freed et al. [70]
	Dopamine neurotransmission	^18F-6-fluorodopa	34 patients with advanced PD	Fetal nigral transplantation	Striatal ^18F-6-DOPA uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination.	Olanow et al. [71]
AD	MAO-B inhibition dopamine neurotransmission	^11C-L-deprenyl-D2	10 AD patients versus 6 elderly control subjects	Sembragiline MAO-B inhibitor	This PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD.	Sturm et al. [74]
	Acetylcholine neurotransmission	^11C-PMP	18 subjects (12 galantamine versus 6 placebo) with mild to moderate AD (14 completed 12 months study)	Galantamine	In the galantamine group, there was significant inhibition of AChE activity in all four cortical regions (frontal, parietal, parietotemporal, temporal).	Kadir et al. [75]
		^11C-nicotine			The placebo group did not show any significant inhibition compared with baseline.
					A positive correlation was observed between changes in the average cortical ^11C nicotine binding and plasma galantamine concentrations.
PD	Serotonin neurotransmission	^11C-DASB	2 PD patients who had shown recovery of motor function after intrastriatal fetal ventral mesencephalic tissue transplantation but experienced off-phase GIDs	Neural transplantation	It was found excessive serotoninergic innervation in the grafted putamen in one patient and putamen and caudate nucleus in second patient.	Politis et al. [73]
				Buspirone 5-HT1A receptor agonist	Buspirone in low repeated dose markedly attenuated dyskinesia severity in both transplanted patients.
SCZ	GABA neurotransmission	^11C-flumazenil	17 off-medication SCZ patients versus 22 HC	Tiagabine	^11C-flumazenil VT was significantly increased across all cortical brain regions in the healthy comparison group but not in the schizophrenia group.	Frankle et al. [72]
				IGAT1
	GABA neurotransmission	^11C-Ro15-4513	12 healthy male completed the Tiagabine challenge study	Tiagabine	Tiagabine administration produced significant reductions in hippocampal, parahippocampal, amygdala, and anterior cingulate synaptic α1 ^11C-Ro15-4513 binding, and a trend significance reduction in the nucleus accumbens.	Stokes et al. [76]
				IGAT1

AChE, acetylcholinesterase; AD, Alzheimer disease; BP, binding potential; DA, dopamine; EC, elderly control; GIDs, graft-induced dyskinesia; HC, healthy comparison; MAO-B, monoamine oxydase type B; IP, idiopathic parkinsonism; LD, levodopa; PET, positron emission tomography; RAC, ¹¹C-raclopride; SCZ, schizophrenia; V_T, tissue distribution volume.