Measuring SSRI occupancy of SERT using the novel tracer [123I]ADAM: a SPECT validation study

Erlandsson, Kjell; Sivananthan, Tharani; Lui, D; Spezzi, Andrea; Townsend, Caroline; Mu, Song; Lucas, Richard; Warrington, Steven; Ell, Peter J.

doi:10.1007/s00259-005-1912-y

Cited by 50 publications

(32 citation statements)

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“…This finding confirms a previous study on baboons that also found the simplified reference tissue model to underestimate specific binding, with an increasing bias for high-density regions (30). The clinical studies published so far have recommended use of a ratio between specific binding regions and cerebellum that includes time-activity curves from 200 to 360 min after injection, with a total acquisition time of 30-60 min (7,9,10,17). This recommendation is based on comparisons with simplified reference tissue model estimates from data generated by sequential acquisitions at 5.5-7 h after injection.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of the Serotonin Transporter Ligand ¹²³I-ADAM for SPECT Studies on Humans

Frøkjær¹,

Pinborg²,

Madsen³

et al. 2008

J Nucl Med

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Imaging serotonin transporters in the living human brain is important in several fields, such as normal psychophysiology, mood disorders, eating disorders, and neurodegenerative disorders. The aim of this study was to compare different kinetic and semiquantitative methods for assessing serotonin transporters using 123 I-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM) in humans: an arterial plasma input model, simplified and Logan reference tissue models, and standardized uptake value ratios. Methods: Nine subjects were scanned with dynamic 123 I-ADAM SPECT (mean age, 31 y; range, 24-43 y), and metabolite-corrected arterial input was measured. Tissue reference models (simplified reference tissue model, Logan reference tissue model, and ratio method) were validated against the outcome of a 1-tissue-compartment model, and performance with decreasing scan length was evaluated. The specificity of 123 I-ADAM binding was investigated in a blocking experiment. Results: Binding estimates from the simplified reference tissue and Logan reference tissue models correlated tightly with full kinetic modeling when based on a 240-or 360-min dynamic acquisition (r 5 0.99); however, there were slight underestimations (3%-5%), especially in high-binding regions. Application of the ratio method to data from 200 to 240 min overestimated specific binding (on average, by 10% 6 28%) and correlated only moderately with estimates from the 1-tissue-compartment model (r 5 0.94). With an acquisition time of 0-120 min, the Logan model still yielded an acceptable outcome when a fixed clearance rate constant (k29) from the cerebellum was applied. Intravenously injected citalopram was not associated with a decrease in cerebellar binding. A lipophilic metabolite that did not seem to bind specifically to serotonin transporter was seen in 2 of 7 subjects. Conclusion: Serotonin transporter binding with 123 I-ADAM SPECT can be assessed with the Logan model based on a 120-min acquisition when a constant k29 is applied. This model, because it allows for more accurate and less biased binding estimates and thus reduces the required sample size, is advantageous over the ratio method used in clinical studies so far. A single blocking experiment supported the use of the cerebellum as a reference region.

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Section: Discussionmentioning

confidence: 99%

“…With the sample sizes of 10-44 subjects used in previous 123 I-ADAM imaging studies, only major differences would be detectable. Accordingly, occupancy calculations based on the ratio method have been highly variable (17).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Serotonin Transporter Ligand ¹²³I-ADAM for SPECT Studies on Humans

Frøkjær¹,

Pinborg²,

Madsen³

et al. 2008

J Nucl Med

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“…Differences in percent 5-HTT occupancy between the strains are also unlikely to explain the observed differences in behavioral response. In humans, therapeutic doses of citalopram (10-60 mg/day) and other SSRIs result in mean 5-HTT occupancies of approximately 75-80% across doses (Erlandsson et al 2005;Meyer et al 2001). To our knowledge, the relationship between and citalopram plasma levels and 5-HTT occupancy in mice has not been reported.…”

Section: Discussionmentioning

confidence: 98%

Antidepressant response to chronic citalopram treatment in eight inbred mouse strains

et al. 2010

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“…SPECT investigations were performed about 210 min after tracer application (Klein et al 2004;Erlandsson et al 2005;Sacher et al 2006). A total of 180 frames (60/camera head) were collected using a step and shoot mode.…”

Section: Spectmentioning

confidence: 99%

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram

et al. 2006

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SPECT and [123I]ADAM were used to investigate SERT occupancies after single doses of escitalopram or citalopram. The test-retest study revealed good reproducibility of SERT quantification. Similar SERT occupancies were found after administration of equal doses (in respect to mg) of escitalopram and citalopram, giving indirect evidence for a fractional blockade of SERT by the inactive R-citalopram.

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Measuring SSRI occupancy of SERT using the novel tracer [123I]ADAM: a SPECT validation study

Abstract: Binding of [123I]ADAM to SERT in midbrain can be quantified with a single scan starting 200 min after injection. However, the variability of estimated occupancy values may be too high for critical assessment of occupancy of SERT by SSRI.

Cited by 50 publications

References 24 publications

Evaluation of the Serotonin Transporter Ligand ¹²³I-ADAM for SPECT Studies on Humans

Evaluation of the Serotonin Transporter Ligand ¹²³I-ADAM for SPECT Studies on Humans

Antidepressant response to chronic citalopram treatment in eight inbred mouse strains

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram

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Measuring SSRI occupancy of SERT using the novel tracer [123I]ADAM: a SPECT validation study

Abstract: Binding of [123I]ADAM to SERT in midbrain can be quantified with a single scan starting 200 min after injection. However, the variability of estimated occupancy values may be too high for critical assessment of occupancy of SERT by SSRI.

Cited by 50 publications

References 24 publications

Evaluation of the Serotonin Transporter Ligand 123I-ADAM for SPECT Studies on Humans

Evaluation of the Serotonin Transporter Ligand 123I-ADAM for SPECT Studies on Humans

Antidepressant response to chronic citalopram treatment in eight inbred mouse strains

In vivo imaging of serotonin transporter occupancy by means of SPECT and [123I]ADAM in healthy subjects administered different doses of escitalopram or citalopram

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Evaluation of the Serotonin Transporter Ligand ¹²³I-ADAM for SPECT Studies on Humans

Evaluation of the Serotonin Transporter Ligand ¹²³I-ADAM for SPECT Studies on Humans