**2.4.2.1 [18F]FDDNP**

2-(1-[6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile

([18F]FDDNP) is a recently developed radiopharmaceutical designed to elucidate brain plaques and NFTs (Small, et al., 2006). Unlike [11C]PiB, [18F]FDDNP can bind to both amyloid-ß plaques as well as tau NFTs, and it has been used in this capacity to quantify NFT and plaque build-up in AD (Small, et al., 2006). Currently [18F]FDDNP is the only biomarker of its kind being studied in human clinical trials, and such trials demonstrated the ability of [18F]FDDNP PET to distinguish healthy control patients from patients with mild cognitive

Diagnosis of Dementia Using Nuclear Medicine Imaging Modalities 215

et al., 1997; Iyo, et al., 1997; Koeppe, et al., 1997; Kuhl, et al., 1996). For example, statistically significant decreases in the cortical hydrolysis rate of [11C]PMP in AD brains, versus agematched controls, have been detected, and correlations identified (Bohnen, et al., 2005; Iyo, et al., 1997; Kilbourn, et al., 1996; Kuhl, et al., 1996). Similar results have also been obtained

Microglial activation is the body's natural response to brain injury and associated neuroinflammation. In addition, microglial activation is also thought to play a significant role in the immune response to AD-related neuronal degeneration and, in AD patients, activated microglia can be found at sites associated with the deposition of aggregated Aβ (Kadir and Nordberg, 2010). There is consequently significant interest in developing radiopharmaceuticals that allow exploration of microglial activation using PET imaging, and the most common are ligands that target the peripheral benzodiazepine receptor including [11C]PK11195 and [11C]PBR28. Cagnin and co-workers reported increased levels of [11C]PK11195 in the entorhinal, temporoparietal, and cingulate cortices in patients with mild AD (when compared to normal controls) (A. Cagnin, et al., 2001). In related work, Edison and colleagues imaged AD patients with both [11C]PK11195 and [11C]PiB. They found a negative correlation between cortical microglial activation and cognition in AD patients, but there was no observable correlation between [11C]PK11195 uptake and [11C]PiB binding

Parkinson's disease (PD) is a progressive degenerative neurological disease, characterized by asymmetric onset of resting tremors, rigidity, and bradykinesia in the limbs, leading ultimately to unstable posture. The disease is less common in adults under 60, but not unheard of, and it does become more common with increasing age. Progression of symptoms in PD typically occurs over 10–30 years, but progression can be accelerated in

The hallmark pathology of Parkinson's disease is loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to striatal dopamine deficiency, and classical symptoms of PD are thought to develop when 80% of striatal dopamine and 50% of the SNc neurons are lost. In addition to dopamine loss, concomitant formation of Lewy bodies also occurs in PD. Lewy bodies are composed primarily of synuclein and appearance of such intraneuronal Lewy body inclusions occurs initially in the lower brainstem and medulla oblongata, followed by midbrain and nigral involvement and, eventually, limbic and association cortical areas. Despite this, Pavese and Brooks indicate that even with the prevalence of Lewy bodies, decline of the dopaminergic system is still the primary factor in PD. Other related Parkinsonian syndromes are known however, and dementia occurs in most of them. For example, Dementia with Lewy bodies (DLB) is a common neurodegenerative dementia that is also associated with the development of α-synuclein positive Lewy body neuronal inclusions in the cortex, substantia nigra and brainstem. Patients with DLB, suffer from progressive cognitive decline including memory loss, visual hallucinations, cognitive circadian fluctuations and sleep disorders. Reflecting the seriousness of these conditions, enormous research has been undertaken to develop

certain individuals, especially those with the so-called Parkinson's-plus syndrome.

using [11C]-*N*-methyl-4-piperidyl-acetate ([11C]AMP) (Namba, et al., 1994).

**2.6 Measurement of neuroinflammation** 

(Edison, et al., 2008).

**3.1 Introduction** 

**3. Parkinsonian dementias** 

impairment, and from patients with AD. Initial studies have shown that patients with AD have significantly more [18F]FDDNP binding in the temporal, parietal, and frontal regions of the brain than the corresponding healthy controls. The non-specificity of [18F]FDDNP, however, appears to have limited its application to date, as the study of this probe has not progressed past these initial clinical studies.
