To scan or not to scan: DaT is the question.

Neurology 2012;78:688–689 The Food and Drug Administration (FDA) recently approved [I]ioflupane ([I]-fluoropropyl CIT), a dopamine transporter (DAT) radioligand, for SPECT to “assist in the evaluation of adult patients with suspected parkinsonian syndromes (PS).”1 This permits physicians to prescribe [I]ioflupane SPECT scans as part of clinical practice. Advertisements encourage clinicians to order this and patients to request such scans. The key questions for neurologists are as follows: Do [I]ioflupane SPECT scans provide useful data beyond clinical evaluation? Does this information improve patient care? SPECT measurement of the striatal uptake of [I]ioflupane reflects the integrity of terminal fields of nigrostriatal neurons. People with Parkinson disease (PD) have reduced striatal uptake.2,3 In fact, such scans may be more sensitive than the clinical examination to detect nigrostriatal defects.4 However, loss of striatal DAT occurs in most degenerative PS, including multisystem atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal disease (CBD).5 Thus, in individual cases, reduced striatal uptake of [I]ioflupane does not distinguish these different conditions. Most clinical studies focused on whether these scans reliably discriminate PS from disorders that clinically resemble PS but without striatal DAT deficiency. Multiple studies report that DAT SPECT can distinguish PS from essential tremor (ET). ET is chosen as the comparator disorder for many studies since it has normal striatal DAT. The first published study compared DAT SPECT with initial and 6-month follow-up examinations by a movement disorders expert.6 The goal was to determine whether SPECT predicts the follow-up clinical diagnosis. The subjects had either PS or other various nondegenerative conditions including ET. Imaging correctly identified 23 of 25 with PS, demonstrating that SPECT is almost as good as the follow-up examination. One might argue that DAT SPECT saves 6 months to make the correct diagnosis. In this issue of Neurology, de la FuenteFernández7 questions the clinical utility of [I]ioflupane SPECT. He analyzed 2 clinical studies submitted to the FDA by GE Healthcare, the manufacturer of [I]ioflupane. The first compared [I]ioflupane SPECT in normal controls with people with PS or ET. The second study compared baseline and 36-month follow-up clinical evaluations by movement disorders experts with SPECT scans. de la Fuente-Fernández calculated sensitivity, specificity, and positive and negative predictive values for the SPECT assuming that clinical diagnoses were “truth” and did the same calculations for the clinical diagnoses assuming that the SPECT data were “truth.” He found nearly identical diagnostic accuracy of clinical diagnosis and SPECT and suggested that the SPECT findings were redundant. This straightforward analysis demonstrates the limited clinical utility of DAT SPECT. This is not surprising since the gold standard for these studies was clinical diagnosis. So what are we to do? First, let’s return to the key questions. In these studies, [I]ioflupane SPECT did not provide utility beyond clinical diagnoses. More importantly, relying on these scans rather than neurologic follow-up may have risk. Several years’ follow-up of people with negative DAT SPECTs reveals that some develop idiopathic PD or another PS.8 If the clinician relied on SPECT for diagnosis, these people would not be treated. Similarly, patients with dopa-responsive dystonia may develop parkinsonism but with normal striatal DAT.9 Reliance on DAT SPECT could cause clinicians to miss this condition that dramatically responds to levodopa. DAT SPECT could lead to other misdiagnoses. Can we