It is suggested that patients should avoid taking any medication or drugs of abuse that may influence visual and quantitative assessment of dopamine transporter scans (Darcourt et al. 2009). Therefore, a medication-free interval of five times the biological half-life is advised. Whether or not patients did adhere to this rule should be checked before injecting the radiopharmaceutical. If medication was not adequately stopped, postponing the investigation is strongly advised.

At least 5 min before tracer injection, the thyroid gland may be blocked by at least 200 mg sodium perchlorate as to prevent excessive free iodine uptake within the thyroid (information leaflet GE Healthcare ^®). The tracers themselves are injected intravenously with a typical dose of 150–250 MBq. The time from injection to start of data acquisition is 18–24 h for β-CIT and 3–6 h for FP-CIT (Darcourt et al. 2009). The information leaflet provided by GE Healthcare ^® states that adverse reactions occurred in less than 1 % of a group of 942 subjects. These consisted of headache, nausea, vertigo, dry mouth or dizziness.

For optimal SPECT imaging, it is important to position the detectors as close as possible to the head of the patient (<13 cm). LEHR or LEUHR collimators on a double-headed gamma camera are preferably used. During acquisition the camera heads rotate 180° (64 views) around the head of the patient. After acquisition, data are reconstructed using filtered back projection (FBP) or iterative reconstruction. If possible, attenuation correction is strongly recommended, using either a calculated homogeneous correction matrix according to Chang or a CT acquired attenuation map (Darcourt et al. 2009).

In addition to visual assessment of images, semiquantitative analysis is strongly recommended as it may lead to more accurate assessment of images (Darcourt et al. 2009).

In both cases, symmetry of striatal DaT binding is assessed and reported. Semiquantitation may also be used in a follow-up setting in case of suspected disease progression or for monitoring of therapy effectiveness.

Quantification is done by drawing a region of interest (ROI) around the striatum and striatal subregions (caudate nucleus, putamen). The ROIs are drawn to calculate specific binding values:

As reference, region-specific regions with known low or absent dopamine transporter uptake are chosen as to assess the amount of nonspecific binding. These regions may consist of occipital cortex and cerebellum. ROIs are drawn using visual contouring, threshold methods or using templates or overlay with an MRI scan. The latter is specifically useful in cases with already visual low to absent dopamine transporter uptake in the striatal region (Darcourt et al. 2009).

The calculated specific binding of striatum and striatal subregions may be compared to the specific binding values of an age-matched normal control group. A significant (linear) decline of 4–7 % per decade with age has been reported (Varrone et al. 2013). However, while Booij et al. also found a significant age-associated decline of [I-123]FP-CIT binding to striatal dopamine transporters in controls, they did not so in parkinsonian patients. This finding might give further support for the existence of an age-independent threshold in PD (Booij et al. 2001). Finally, while gender differences related to oestrogen levels have been noted in PD, we are not aware of databases taking into account these differences in clinical evaluation (Haaxma et al. 2007).

PET scans using 6-[¹⁸F]-fluoro-L-3,4-dihydroxyphenylalanine (¹⁸F-FDOPA) allow quantification of striatal DOPA decarboxylase activity and storage capacity of ¹⁸F-dopamine.

The use of catechol-O-methyltransferase (COMT) inhibitors should be ceased before the PET scan. It is however highly recommended to let the patient fast for at least 24 h, with particular attention for reducing amino acid uptake. Prior to the intravenous injection of 100–200 MBq ¹⁸F-FDOPA, the patient receives 2 mg/kg carbidopa (a peripheral AADC inhibitor), with a maximum of 150 mg, in order to increase plasma availability of the tracer to organs other than the pancreas. The acquisition consists of a 3D static imaging after 90 min, with 6 min acquisition time. Images are corrected for attenuation similar to SPECT investigations. The data analysis is both visually and quantitatively, in which case ROIs are drawn around striatum and striatal subregions (Eidelberg et al. 1990; Ishikawa et al. 1996; Eshuis et al. 2006).

The major differences between DaT-SPECT and ¹⁸F-FDOPA PET are listed in Table 27.2.

First of all, it has been suggested that loss of dopamine transporters in PD may be more severe than loss of dopaminergic neurons and thus may cause an increase in SPECT sensitivity (Lavalaye et al. 2000; van Dyck et al. 2006). Whereas the plasma membrane DA transporter is downregulated in the striatum of patients with PD, a study by Lee et al. suggested that the activity of aromatic L-amino acid decarboxylase is upregulated (Lee et al. 2000).

Two clinical studies, however, showed a good correlation between the specific binding values of FP-CIT and ¹⁸F-DOPA PET in patients with known PD (Ishikawa et al. 1996; Eshuis et al. 2006). Eshuis et al. also found no significant difference in their capacity to differentiate between de novo and advanced patients. These studies suggest that in clinical practice accuracy may be similar. On the other hand, comparative studies are limited, and thus, a conclusive statement with regard to the superiority of one scan over the other may not be possible.

Despite their relative (dis)advantages, in practice ‘couleur locale’, such as experience or availability, will most likely determine which of the two techniques is used.

The primary and secondary indications for ¹²³I-labelled iodobenzamide (¹²³I-IBZM) are summarized in Table 27.3. As with FP-CIT, the basis of this summary will be briefly discussed.

In 2002 a procedure guideline for using ¹²³I-labelled dopamine D₂ receptor ligands was published by the EANM task group. As ‘common indication’ was stated the differential diagnosis of parkinsonian syndromes: ‘a major indication is to distinguish PD from other parkinsonian syndromes (e.g. MSA or PSP)’ (Tatsch et al. 2002).

The EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2 receptor ligands, version 2 were published by Van Laere et al. in 2009 (Van Laere et al. 2009).

Aims of these guidelines were to assist nuclear medicine practitioners in making recommendations, performing, interpreting and reporting the results of clinical dopamine D2 receptor SPECT or PET studies, and to achieve a high quality standard of dopamine D2 receptor imaging, to increase the impact of this technique in neurological practice. The document was conceived as an update of the first guidelines for SPECT using D2 receptor ligands labelled with ¹²³I and was guided by the views of the Society of Nuclear Medicine Brain Imaging Council and the individual experience of experts in European countries. ‘The main indication is the differentiation of Parkinson’s disease from other neurodegenerative parkinsonian syndromes characterized by loss of D2 receptors (e.g. multiple system atrophy and progressive supranuclear palsy). Several recent reports show that the use of D2 imaging alone may not be highly sensitive’ (Van Laere et al. 2009).