Childhood and adolescence disorders Pre-treatment and post-treatment Tc-99m TRODAT-1 brain spect findings in three patients with attention deficit and hyperactivity disorder, who were treated by 2-month- atomoxetine treatment

Objective: Tc-99m TRODAT-1 has a high affinity and specifity as an agent for presynaptic DAT in the striatal dopamine nerve terminal. Effectivity of Tc-99m TRODAT-1 for qualification of striatal DAT has been studied in a majority of related publications. Although some studies found the increase of DAT receptor binding in patients with attention deficit hyperactivity disorder (ADHD) compared to the normal controls, some of them did not find any increase. Atomoxetine is a selective inhibitor of the presynaptic norepinephrine transporter, with minimal affinity for other neurotransmitter transporters and receptors. We have planned to report post-treatment changes in Tc-99m TRODAT-1 brain SPECT of 3 adolescents (13-17 years), who were followed up for the diagnosis of ADHD and received atomoxetine treatment for 2 months.

Method: All patients were right handed. ADHD diagnosis were made by two experienced pediatric psychiatrists, based on the ADHD criteria listed in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). K-SADS-PL semi-structured clinical interview had been carried out. ADHD diagnosis had to be confirmed and CGI-ADHD-severity scale had to be >=3 at visit 1. DuPaul ADHD Questionnaire and Conner’s Teacher Rating Scale-Short Form were used. Neurological examinations and ECG records of all patients were normal without any severe anatomic pathology in brain MRIs. IQ values were over 80. Except specific learning disorder and oppositional defiant behavior disorder, other psychological disorders have been excluded. Tc-99m TRODAT-1 brain SPECT images have been obtained before and after the treatment. Brain SPECT imaging has been performed 3 hours after the I.V. injection of 740 MBq Tc-99m TRODAT-1 (Nuclear Energy Institute, Taiwan); which was in lyophilized form and was radio-labelled with Tc-99m pertechnetate (radiochemical purity %90 and over). Tc-99m TRODAT-1 brain SPECT images were evaluated.

Results: Tc-99m TRODAT-1 involvements were evaluated semiquantitatively as above the scalp activity, equivalent to scalp activity and below the scalp activity in the basal ganglion. Decreases especially in DuPaul total and DuPaul attention scales have been observed among postoperative scales. Tc-99m TRODAT-1 involvement in the basal ganglion has decreased in all 3 subjects in SPECT.

Conclusion: Tc-99m TRODAT-1 demonstrates high affinity and specificity to presynaptic DAT receptors in striatal dopaminergic nerve terminals. Its efficacy in identification of striatal DAT has been demonstrated in previous studies. After 2-month- chronic treatment with atomoxetine, decreased involvements in basal ganglion in all 3 subjects have indicated that atomoxetine might indirectly affect striatal dopaminergic pathways. Despite the limited number of patients, we believe that this finding is significant since there is no information about basal ganglion imaging in patients receiving atomoxetine.