TY - JOUR
T1 - Serotonin transporters in dopamine transporter imaging: a head-to-head comparison of dopamine transporter SPECT radioligands 123I-FP-CIT and 123I-PE2I
AU - Ziebell, Morten
AU - Holm-Hansen, Signe
AU - Thomsen, Gerda
AU - Wagner, Aase
AU - Jensen, Peter
AU - Pinborg, Lars H
AU - Knudsen, Gitte Moos
PY - 2010/12/1
Y1 - 2010/12/1
N2 - 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 123I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3- fluoropropyl)nortropane (123I-FP-CIT) and 123I-N-(3- iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) ( 123I-PE2I). 123I-FP-CIT has a 10-fold higher selectivity than 123I-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: 123I-FP-CIT was given as a bolus injection, and the ratio between the striatum and reference tissue was measured after 3 h. 123I-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 123I-FP-CIT was on average 18% higher than the striatal BP ND of 123I-PE2I. Equal doses of radioactivity resulted in 3 times higher counting rates for 123I-FP-CIT than for 123I-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) 123I-FP-CIT binding ratios, whereas BPND of 123I-PE2I was unaltered. Likewise, blocking of SERT led to increased (21% ± 30.1%, P < 0.001) plasma 123I-FP-CIT, probably as a result of significant blocking of peripheral SERT binding sites. By contrast, plasma 123I-PE2I remained stable. Conclusion: 123I-FP-CIT and 123I-PE2I had approximately the same target-to-background ratios, but per injected megabecquerel, 123I-FP-CIT gave rise to 3-fold higher cerebral counting rates. We found that 123I-FP-CIT, but not 123I-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.
AB - 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 123I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3- fluoropropyl)nortropane (123I-FP-CIT) and 123I-N-(3- iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) ( 123I-PE2I). 123I-FP-CIT has a 10-fold higher selectivity than 123I-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: 123I-FP-CIT was given as a bolus injection, and the ratio between the striatum and reference tissue was measured after 3 h. 123I-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 123I-FP-CIT was on average 18% higher than the striatal BP ND of 123I-PE2I. Equal doses of radioactivity resulted in 3 times higher counting rates for 123I-FP-CIT than for 123I-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) 123I-FP-CIT binding ratios, whereas BPND of 123I-PE2I was unaltered. Likewise, blocking of SERT led to increased (21% ± 30.1%, P < 0.001) plasma 123I-FP-CIT, probably as a result of significant blocking of peripheral SERT binding sites. By contrast, plasma 123I-PE2I remained stable. Conclusion: 123I-FP-CIT and 123I-PE2I had approximately the same target-to-background ratios, but per injected megabecquerel, 123I-FP-CIT gave rise to 3-fold higher cerebral counting rates. We found that 123I-FP-CIT, but not 123I-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.
U2 - 10.2967/jnumed.110.078337
DO - 10.2967/jnumed.110.078337
M3 - Journal article
SN - 0161-5505
VL - 51
SP - 1885
EP - 1891
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 12
ER -