Serotonin Transporters in Dopamine Transporter Imaging: A Head-to-Head Comparison of Dopamine Transporter SPECT Radioligands I-123-FP-CIT and I-123-PE2I

Current SPECT radioligands available for in vivo imaging of the dopamine transporter (DAT) also show affinity for monoamine transporters other than DAT, especially the serotonin transporter (SERT). The effect of this lack of selectivity for in vivo imaging is unknown. In this study, we compared the SPECT radioligands I-123-2-beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (I-123-FP-CIT) and I-123-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3 beta-(4-methylphenyl) (I-123-PE2I). I-123-FP-CIT has a 10-fold higher selectivity than I-123-FP-CIT for DAT versus SERT. Methods: Sixteen healthy individuals were scanned in random order with both radioligands. The radioligands were administered according to standard recommendations: I-123-FP-CIT was given as a bolus injection, and the ratio between the striatum and reference tissue was measured after 3 h. I-123-PE2I was administered in a bolus-infusion setup, and the nondisplaceable binding potential (BPND) was measured after 2 h. To assess the contribution of SERT to the overall SPECT signal, SERT was blocked by intravenous citalopram in 6 of the individuals. Results: The striatum-to-reference ratio - 1 of I-123-FP-CIT was on average 18% higher than the striatal BPND of I-123-PE2I. Equal doses of radioactivity resulted in 3 times higher counting rates for I-123-FP-CIT than for I-123-PE2I, both in target and in reference brain regions. Citalopram infusion led to significant reductions in both striatal (22.8% +/- 20.4%, P < 0.05) and thalamic (63.0% +/- 47.9%, P < 0.05) I-123-FP-CIT binding ratios, whereas BPND of I-123-PE2I was unaltered. Likewise, blocking of SERT led to increased (21% +/- 30.1%, P < 0.001) plasma I-123-FP-CIT, probably as a result of significant blocking of peripheral SERT binding sites. By contrast, plasma I-123-PE2I remained stable. Conclusion: I-123-FP-CIT and I-123-PE2I had approximately the same target-to-background ratios, but per injected megabecquerel, I-123-FP-CIT gave rise to 3-fold higher cerebral counting rates. We found that I-123-FP-CIT, but not I-123-PE2I, brain images have a highly interindividual but significant signal contribution from SERT. Whether the SERT signal contribution is of clinical importance needs to be established in future patient studies.