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|Molecular weight||282.392014 g/mol|
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DASB is a compound that binds to the serotonin transporter. Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography (PET) since around year 2000. In this context it is regarded as one of the superior radioligands for PET study of the serotonin transporter in the brain, since it has high selectivity for the serotonin transporter.
The DASB image from a human PET scan shows high binding in the midbrain, thalamus and striatum, moderate binding in the medial temporal lobe and anterior cingulate, and low binding in neocortex. The cerebellum is often regarded as a region with no specific serotonin transporter binding and the brain region is used as a reference in some studies.
Since the serotonin transporter is the target of SSRIs used in the treatment of major depression it has been natural to examine DASB binding in depressed patients. Several such research studies have been performed.
There are a number of alternative PET radioligands for imaging the serotonin transporter: [11C]ADAM, [11C]AFM, [11C]DAPA, [11C]McN5652, and [11C]-NS 4194. A related molecule to DASB, that can be labeled with fluorine-18, has also been suggested as a PET radioligand. With single-photon emission computed tomography (SPECT) using the radioisotope iodine-123 there are further radioligands available: [123I]ODAM, [123I]IDAM, [123I]ADAM, and [123I]β-CIT. A few studies have examined the difference in binding between the radioligands in nonhuman primates, as well as in pigs.
Methodological issues Edit
When the DASB neuroimages are analyzed the kinetic models suggested by Ichise and coworkers can be employed to estimate the binding potential. A test-retest reproducibility experiment has been performed to evaluate this approach.
Besides the studies listed below a few occupancy studies have been reported.
|5-HTTLPR LALA serotonin transporter genotype||Increase in putamen||43/30|||
|5-HTTLPR LALA serotonin transporter genotype||Increase in midbrain||19|||
|Age||No effect found|| ()|
|Body mass index||Inverse correlation (?)||?|||
|Seasonality||Higher in winter in putamen and caudate||54|||
|Seasonality||Higher in fall and winter||88|||
|NEO PI-R Neuroticism||Positive correlation in thalamus||31 males|||
|Depressed during major depressive episodes||No difference found||20+20|||
|Depressed with highly negativistic "dysfunctional attitudes" during major depressive episodes||Increase in prefrontal cortex, anterior cingulate, thalamus, bilateral caudate, and bilateral putamen||20(?)+20|||
|Recovered depressed patients||No difference found||24+20 males|||
|Unipolar depression||Increase in thalamus, insula and striatum||18+34|||
|Unmedicated unipolar major depression||Reduced 5-HTT availability in the thalamus|||
|TCI anxiety in unmedicated unipolar major depression||Reduced 5-HTT availability in the thalamus, midbrain and amygdala|||
|Bipolar depression||Increase in thalamus, insula and striatum||18+34|||
|Bipolar depression||Decrease in midbrain, amygdala, hippocampus, thalamus, putamen, and anterior cingulate cortex||18+41|||
|Obsessive compulsive disorder||Reduction and correlation with severity in thalamus and midbrain||9+19|||
|Alcoholism||No significant alteration||30 + 18|||
|Parkinson's disease||Reduction in forebrain||5+8|||
|Non-depressed Parkinson's disease||Decreased binding in caudate, midbrain, putamen, orbitofrontal cortex and (non-significantly) dorsolateral prefrontal cortex|||
|Depressed Parkinson's disease patients||Increase in prefrontal and dorsolateral cortices||7+7|||
|Abstinent MDMA ('Ecstasy') users||Global reduction||23+19|||
|Reduced synaptic serotonin (by rapid tryptophan depletion)||(small reduction in binding potential)||8|||
|Lowering of brain serotonin (by acute tryptophan depletion)||No change observed||25 (14)|||
- ↑ S. Houle, N. Ginovart, D. Hussey, J.H. Meyer, A.A. Wilson (October 2000). Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB. European Journal of Nuclear Medicine and Molecular Imaging 27 (11): 1719.
- ↑ 2.0 2.1 2.2 Peter Brust, Swen Hess and Ulrich Müller and Zsolt Szabo (February 2006). Neuroimaging of the Serotonin Transporter — Possibilities and Pitfalls. Current Psychiatry Reviews 2 (1): 111–149.
- ↑ Alan A. Wilson, Nathalie Ginovart, Doug Hussey, Jeff Meyer & Sylvain Houle (July 2002). In vitro and in vivo characterisation of [11C]-DASB: a probe for in vivo measurements of the serotonin transporter by positron emission tomography. Nuclear Medicine and Biology 29 (5): 509–515.
- ↑ 4.0 4.1 W. Gordon Frankle, Mark Slifstein, Roger N. Gunn, Yiyun Huang, Dah-Ren Hwang, E. Ashlie Darr, Rajesh Narendran, Anissa Abi-Dargham and Marc Laruelle (May 2006). Estimation of Serotonin Transporter Parameters with 11C-DASB in Healthy Humans: Reproducibility and Comparison of Methods. Journal of Nuclear Medicine 47 (5): 815–826.
- ↑ 5.0 5.1 Jeffrey H. Meyer (March 2007). Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. Journal of Psychiatry & Neuroscience 32 (2): 86–82.
- ↑ Sudha Garg, Shankar R. Thopate, Richard C. Minton, Kimberly W. Black, Andrew J. H. Lynch, and Pradeep K. Garg (September-October 2007). 3-Amino-4-(2-((4-[18F]fluorobenzyl)methylamino)methylphenylsulfanyl)benzonitrile, an F-18 fluorobenzyl analogue of DASB: synthesis, in vitro binding, and in vivo biodistribution studies. Bioconjug Chem. 18 (5): 1612–1618.
- ↑ Zsolt Szabo, Una D. McCann, Alan A. Wilson, Ursula Scheffel, Taofeek Owonikoko, William B. Mathews, Hayden T. Ravert, John Hilton, Robert F. Dannals,and George A. Ricaurte (May 2002). Comparison of (+)-11C-McN5652 and 11C-DASB as Serotonin Transporter Radioligands Under Various Experimental Conditions. Journal of Nuclear Medicine 43 (5): 678–692.
- ↑ Yiyun Huang, Dah-Ren Hwang, Raj Narendran, Yasuhiko Sudo, Rano Chatterjee, Sung-A Bae, Osama Mawlawi, Lawrence S. Kegeles, Alan A. Wilson, Hank F. Kung and Marc Laruelle (2002). Comparative Evaluation in Nonhuman Primates of Five PET Radiotracers for Imaging the Serotonin Transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM. Journal of Cerebral Blood Flow & Metabolism 22: 1377–1398.
- ↑ Svend B. Jensen, Donald F. Smith, Dirk Bender, Steen Jakobsen, Dan Peters, Elsebet Ø. Nielsen, Gunnar M. Olsen, Jørgen Scheel-Krüger, Alan Wilson, Paul Cumming (May 2003). [11C]-NS 4194 versus [11C]-DASB for PET imaging of serotonin transporters in living porcine brain. Synapse 49 (3): 170–177.
- ↑ Nathalie Ginovart, Alan A. Wilson, Jeffrey H. Meyer, Doug Hussey and Sylvain Houle (2001). Positron Emission Tomography Quantification of [11C]-DASB Binding to the Human Serotonin Transporter: Modeling Strategies. Journal of Cerebral Blood Flow & Metabolism 21: 1342–1353.
- ↑ Masanori Ichise, Jeih-San Liow, Jian-Qiang Lu, Akihiro Takano, Kendra Model, Hiroshi Toyama, Tetsuya Suhara, Kazutoshi Suzuki, Robert B Innis and Richard E Carson (2003). Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain. Journal of Cerebral Blood Flow & Metabolism 23: 1096–1112.
- ↑ Jae Seung Kim, Masanori Ichise, Janet Sangare, and Robert B. Innis (2006). PET Imaging of Serotonin Transporters with [11C]DASB: Test–Retest Reproducibility Using a Multilinear Reference Tissue Parametric Imaging Method. Journal of Nuclear Medicine 47 (2): 208–214.
- ↑ Nicole Praschak-Rieder, J. Kennedy, A. Wilson, D. Hussey, A. Boovariwala, M. Willeit, N. Ginovart, S. Tharmalingam, M. Masellis, S. Houle & Jeffrey H. Meyer (August 2007). Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen: a [11C] DASB positron emission tomography study. Biological Psychiatry 62 (4): 327–331.
- ↑ M. Reimold, M. N. Smolka, G. Schumann, A. Zimmer, J. Wrase, K. Mann, X.-Z. Hu, D. Goldman, G. Reischl, C. Solbach, H.-J. Machulla, R. Bares1 and A. Heinz (May 2007). Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype. Journal of Neural Transmission 114 (5): 635.
- ↑ 15.0 15.1 15.2 Jeffrey H. Meyer, Sylvain Houle, Sandra Sagrati, Anna Carella, Doug F. Hussey, Nathalie Ginovart, Verdell Goulding, James Kennedy, Alan A. Wilson (December 2004). Brain Serotonin Transporter Binding Potential Measured With Carbon 11–Labeled DASB Positron Emission Tomography. Effects of Major Depressive Episodes and Severity of Dysfunctional Attitudes. Archives of General Psychiatry 61 (12): 1271.
- ↑ Ryohei Matsumoto, H. Ito, H. Takahashi, H. Takano and T. Suhara (2008). Inverse correlation between body mass index and serotonin transporter binding in human brain: A [11C]DASB PET study. NeuroImage 2, supplement 2: T161. Neuroreceptor Mapping 2008, The Seventh International Symposium on Functional Neuroreceptor Mapping of Living Brain
- ↑ Jan Kalbitzer, David Erritzoe, Klaus K. Holst, Finn Å. Nielsen, Lisbeth Marner, Szabolcs Lehel, Tine Arentzen, Terry L. Jernigan, & Gitte M. Knudsen. Seasonal changes in brain serotonin transporter binding in short 5-HTTLPR-allele carriers but not in long-allele homozygotes. Nature Precedings.
- ↑ Nicole Praschak-Rieder, Matthaeus Willeit, Alan A. Wilson, Sylvain Houle & Jeffrey H. Meyer (September 2008). Seasonal variation in human brain serotonin transporter binding. Archives of general psychiatry 65 (9): 1072–1078.
- ↑ Akihiro Takano, Ryosuke Arakawaa, Mika Hayashia, Hidehiko Takahashia, Hiroshi Itoa & Tetsuya Suhara (September 2007). Relationship between neuroticism personality trait and serotonin transporter binding. Biological Psychiatry 62 (6): 588–592.
- ↑ Zubin Bhagwagar, Naga Murthy, Sudhakar Selvaraj, Rainer Hinz, Matthew Taylor, Sabrina Fancy, Paul Grasby, and Philip Cowen (December 2007). 5-HTT Binding in Recovered Depressed Patients and Healthy Volunteers: A Positron Emission Tomography Study With [11CDASB]. The American Journal of Psychiatry 164: 1858–1865.
- ↑ 21.0 21.1 Dara M. Cannon, Masanori Ichise, Denise Rollis, Jacqueline M. Klaver, Shilpa K. Gandhi, Dennis S. Charney, Husseini K. Manji and Wayne C. Drevets (October 2007). Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder. Biological Psychiatry 62 (8): 870–877.
- ↑ 22.0 22.1 Matthias Reimold, Batra A, Knobel A, Smolka MN, Zimmer A, Mann K, Solbach C, Reischl G, Schwärzler F, Gründer G, Machulla HJ, Bares R, A. Heinz (2008). Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression: a [11C]DASB PET study. Molecular Psychiatry 13: 606.. Electronic publication
- ↑ Maria A. Oquendo; Ramin S. Hastings; Yung-yu Huang; Norman Simpson; R. Todd Ogden; Xian-zhang Hu; David Goldman; Victoria Arango; Ronald L. Van Heertum; J. John Mann; Ramin V. Parsey (February 2007). Brain Serotonin Transporter Binding in Depressed Patients With Bipolar Disorder Using Positron Emission Tomography. Archives of General Psychiatry 64 (2): 201–208.
- ↑ M. Reimold, M. N. Smolka, A. Zimmer, A. Batra, A. Knobel, C. Solbach, A. Mundt, H. U. Smoltczyk, D. Goldman, K. Mann, G. Reischl, H.-J. Machulla, R. Bares and A. Heinz (December 2007). Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [11C]DASB PET study. Journal of Neural Transmission 114 (12): 1603–1609.
- ↑ Amira K. Brown, David T. George, Masahiro Fujita, Jeih-San Liow, Masanori Ichise, Joseph Hibbeln, Subroto Ghose, Janet Sangare, Daniel Hommer & Robert B. Innis (January 2007). PET [11C]DASB imaging of serotonin transporters in patients with alcoholism. Alcohol Clin Exp Res. 31 (1): 28–32.
- ↑ Roger L Albin, Robert A. Koeppe, Nicolaas I. Bohnen, Kristine Wernette, Michael A. Kilbourn and Kirk A. Frey (2008). Spared caudal brainstem SERT binding in early Parkinson's disease. Journal of Cerebral Blood Flow & Metabolism 28: 441–444.
- ↑ M. Guttman, I. Boileau, J. Warsh, J. A. Saint-Cyr, N. Ginovart, T. McCluskey, S. Houle, A. Wilson, E. Mundo, P. Rusjan, J. Meyer & S. J. Kish (May 2007). Brain serotonin transporter binding in non-depressed patients with Parkinson's disease. European Journal of Neurology 14 (5): 523–528.
- ↑ Isabelle Boileau, Jerry J. Warsh, Mark Guttman, Jean A. Saint-Cyr, Tina McCluskey, Pablo Rusjan, Sylvain Houle, Alan A. Wilson, Jeffrey H. Meyer, Stephen J. Kish (July 2008). Elevated serotonin transporter binding in depressed patients with Parkinson's disease: A preliminary PET study with [(11)C]DASB. Movement Disorders 23: 1776.
- ↑ Una D McCann, Zsolt Szabo, Esen Seckin, Peter Rosenblatt, William B Mathews, Hayden T Ravert, Robert F Dannals and George A Ricaurte (2005). Quantitative PET Studies of the Serotonin Transporter in MDMA Users and Controls Using [11C]McN5652 and [11C]DASB. Neuropsychopharmacology 30: 1741–1750.
- ↑ Peter S. Talbot, W. Gordon Frankle, Dah-Ren Hwang, Yiyun Huang, Raymond F. Suckow, Mark Slifstein, Anissa Abi-Dargham & Marc Laruelle (2004). Effects of reduced endogenous 5-HT on the in vivo binding of the serotonin transporter radioligand 11C-DASB in healthy humans. Synapse 55 (3): 164–175.
- ↑ Nicole Praschak-Riedera, Alan A. Wilson, Douglas Hussey, Anna Carella, Corie Wei, Nathalie Ginovart, Markus J. Schwarz, Johanna Zach, Sylvain Houle and Jeffrey H. Meyer (November 2005). Effects of Tryptophan Depletion on the Serotonin Transporter in Healthy Humans. Biological Psychiatry 58 (10): 825–830.
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