Quantification of cortical DA receptors with [11C]FLB 457 (draft)

[11C]FLB 457 (Halldin et al., 1995) is a high affinity D2/D3 receptor PET radioligand, which can be used to measure cortical (extrastriatal) D2/D3 receptors (Olsson et al., 2004; Sudo et al., 2001; Suhara et al., 1999; Vilkman et al., 2000). [11C]raclopride is another much used PET radioligand to quantify D2/D3 receptors, but it does not provide sufficient signal-to-noise ratio to quantify dopamine receptors in extrastriatal areas; but then [11C]FLB 457 can not be used to quantify dopamine binding in the striatum.

It remains controversial whether [11C]FLB 457 can also be used to quantify cortical DA function, that is, to measure acute changes in synaptic dopamine concentration; there are studies that support this application (Montgomery et al., 2007; Narendran et al., 2009, 2013 and 2014; Ko et al., 2009) and studies where [11C]FLB 457 was not found suitable for this purpose (Okauchi et al., 2001; Aalto et al., 2009).

Suggested analysis method for Turku

Please read the articles from Turku PET Centre.


Aalto S, Hirvonen J, Kaasinen V, Hagelberg N, Kajander J, Någren K, Seppälä T, Rinne JO, Scheinin H, Hietala J. The effects of d-amphetamine on extrastriatal dopamine D2/D3 receptors: a randomized, double-blind, placebo-controlled PET study with [11C]FLB 457 in healthy subjects. Eur J Nucl Med Mol Imaging. 2009; 36(3): 475-483.

Asselin MC, Montgomery AJ, Grasby PM, Hume SP. Quantification of PET studies with the very high-affinity dopamine D2/D3 receptor ligand [11C]FLB 457: re-evaluation of the validity of using a cerebellar reference region. J Cereb Blood Flow Metab. 2007; 27(2): 378-392.

Cselényi Z, Olsson H, Halldin C, Gulyás B, Farde L. A comparison of recent parametric neuroreceptor mapping approaches based on measurements with the high affinity PET radioligands [11C]FLB 457 and [11C]WAY 100635. Neuroimage 2006; 32: 1690-1708.

Farde L, Suhara T, Nyberg S, Karlsson P, Nakashima Y, Hietala J, Halldin C. A PET-study of [11C]FLB 457 binding to extrastriatal D2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients. Psychopharmacology (Berl). 1997; 133(4): 396-404.

Hagelberg N, Aalto S, Kajander J, Oikonen V, Hinkka S, Någren K, Hietala J, Scheinin H. Alfentanil increases cortical dopamine D2/D3 receptor binding in healthy subjects. Pain 2004; 109(1-2): 86-93.

Halldin C, Farde L, Högberg T, Mohell N, Hall H, Suhara T, Karlsson P, Nakashima Y, Swahn CG. Carbon-11-FLB 457: A radioligand for extrastriatal D2 dopamine receptors. J Nucl Med. 1995; 36: 1275–1281.

Hirvonen MM, Lumme V, Hirvonen J, Pesonen U, Någren K, Vahlberg T, Scheinin H, Hietala J. C957T polymorphism of the human dopamine D2 receptor gene predicts extrastriatal dopamine receptor availability in vivo. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33(4): 630-636.

Ikoma Y, Ito H, Arakawa R, Okumura M, Seki C, Shidahara M, Takahashi H, Kimura Y, Kanno I, Suhara T. Error analysis for PET measurement of dopamine D2 receptor occupancy by antipsychotics with [11C]raclopride and [11C]FLB 457. Neuroimage 2008; 42(4): 1285-1294.

Ito H, Sudo Y, Suhara T, Okubo Y, Halldin C, Farde L. Error analysis for quantification of [11C]FLB 457 binding to extrastriatal D2 dopamine receptors in the human brain. Neuroimage 2001; 13(3):531-539.

Kaasinen V, Vilkman H, Hietala J, Någren K, Helenius H, Olsson H, Farde L, Rinne J. Age-related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain. Neurobiol Aging. 2000; 21(5): 683-638.

Ko JH, Ptito A, Monchi O, Cho SS, Van Eimeren T, Pellecchia G, Ballanger B, Rusjan P, Houle S, Strafella AP. Increased dopamine release in the right anterior cingulate cortex during the performance of a sorting task: A [11C]FLB 457 PET study. Neuroimage 2009; 46: 516-521.

Montgomery AJ, Asselin MC, Farde L, Grasby PM. Measurement of methylphenidate-induced change in extrastriatal dopamine concentration using [11C]FLB 457 PET. J Cereb Blood Flow Metab. 2007; 27(2): 369-377.

Narendran R, Frankle WG, Mason NS, Rabiner EA, Gunn RN, Searle GE, Vora S, Litschge M, Kendro S, Cooper TB, Mathis CA, Laruelle M. Positron emission tomography imaging of amphetamine-induced dopamine release in the human cortex: A comparative evaluation of the high affinity dopamine D2/3 radiotracers [11C]FLB 457 and [11C]fallypride. Synapse 2009; 63(6): 447-461.

Narendran R, Mason NS, May MA, Chen CM, Kendro S, Ridler K, Rabiner EA, Laruelle M, Mathis CA, Frankle WG. Positron emission tomography imaging of dopamine D2/3 receptors in the human cortex with [11C]FLB 457: reproducibility studies. Synapse 2011; 65(1): 35-40.

Narendran R, Mason NS, Chen CM, Himes M, Keating P, May MA, Rabiner EA, Laruelle M, Mathis CA, Frankle WG. Evaluation of dopamine D2/3 specific binding in the cerebellum for the positron emission tomography radiotracer [11C]FLB 457: implications for measuring cortical dopamine release. Synapse 2011; 65(10): 991-997.

Narendran R, Himes M, Mason NS. Reproducibility of post-amphetamine [11C]FLB 457 binding to cortical D2/3 receptors. PLoS One 2013; 8(9): e76905.

Narendran R, Jedema HP, Lopresti BJ, Mason NS, Gurnsey K, Ruszkiewicz J, Chen CM, Deuitch L, Frankle WG, Bradberry CW. Imaging dopamine transmission in the frontal cortex: a simultaneous microdialysis and [11C]FLB 457 PET study. Mol Psychiatry 2014; 19(3): 302-310.

Okauchi T, Suhara T, Maeda J, Kawabe K, Obayashi S, Suzuki K. Effect of endogenous dopamine on endogenous dopamine on extrastriated [11C]FLB 457 binding measured by PET. Synapse 2001; 41(2): 87-95.

Okubo Y, Olsson H, Ito H, Lofti M, Suhara T, Halldin C, Farde L. PET mapping of extrastriatal D2-like dopamine receptors in the human brain using an anatomic standardization technique and [11C]FLB 457. Neuroimage 1999; 10(6): 666-674.

Olsson H, Halldin C, Swahn CG, Farde L. Quantification of [11C]FLB 457 binding to extrastriatal dopamine receptors in the human brain. J Cereb Blood Flow Metab. 1999; 19(10): 1164-1173.

Olsson H, Farde L. Potentials and pitfalls using high affinity radioligands in PET and SPET determinations on regional drug induced D2 receptor occupancy - a simulation study based on experimental data. Neuroimage 2001; 14(4): 936-945.

Olsson H, Halldin C, Farde L. Differentiation of extrastriatal dopamine D2 receptor density and affinity in the human brain using PET. Neuroimage 2004; 22(2): 794-803.

Sudo Y, Suhara T, Inoue M, Ito H, Suzuki K, Saijo T, Halldin C, Farde L. Reproducibility of [11C]FLB 457 binding in extrastriatal regions. Nucl Med Commun. 2001; 22(11): 1215-1221.

Suhara T, Sudo Y, Okauchi T, Maeda J, Kawabe K, Suzuki K, Okubo Y, Nakashima Y, Ito H, Tanada S, Halldin C, Farde L. Extrastriatal dopamine D2 receptor density and affinity in the human brain measured by 3D PET. Int J Neuropsychopharmacol. 1999; 2(2): 73-82.

Vilkman H, Kajander J, Någren K, Oikonen V, Syvälahti E, Hietala J. Measurement of extrastriatal D2-like receptor binding with [11C]FLB 457 - a test-retest analysis. Eur J Nucl Med. 2000; 27(11): 1666-1673.

Tags: ,

Updated at: 2014-10-08
Created at: 2007-12-03
Written by: Vesa Oikonen