TY - JOUR
T1 - Evaluation of the Serotonin Transporter Ligand 123I-ADAM for SPECT Studies on Humans
AU - Frokjaer, V.G.
AU - Pinborg, Lars Hageman
AU - Madsen, J.
AU - de Nijs, Robin
AU - Svarer, C.
AU - Wagner, A.
AU - Knudsen, Gitte Moos
PY - 2008
Y1 - 2008
N2 - 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 = 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% +/- 28%) and correlated only moderately with estimates from the 1-tissue-compartment model (r = 0.94). With an acquisition time of 0-120 min, the Logan model still yielded an acceptable outcome when a fixed clearance rate constant (k2') 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 k2' 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
Udgivelsesdato: 2008/2
AB - 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 = 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% +/- 28%) and correlated only moderately with estimates from the 1-tissue-compartment model (r = 0.94). With an acquisition time of 0-120 min, the Logan model still yielded an acceptable outcome when a fixed clearance rate constant (k2') 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 k2' 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
Udgivelsesdato: 2008/2
U2 - 10.2967/jnumed.107.046102
DO - 10.2967/jnumed.107.046102
M3 - Journal article
C2 - 18199621
SN - 0161-5505
VL - 49
SP - 247
EP - 254
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 2
ER -