LBT-999
Molecule in development
Parkinson’s disease, second most common neurodegenerative pathology in the world
Parkinson’s disease is a chronicle neurodegenerative disease affecting the central nervous system, responsible for disorders, being mostly motor disorders with progressive evolution.
Females and males are at risk, with an average age for the onset of the disease between 45 and 60. Anatomically, Parkinson’s disease is characterized by the selective degeneration of dopaminergic neurons (i.e. producing dopaminergic neurotransmitter) reaching the striatum. Functionally, the dopamine level reduces in the synaptic cleft of dopaminergic neurons.
people are living with Parkinson’s disease in the world
new cases in the US per year
Source:
Parkinson’s Foundation, parkinson.org
LBT-999, a specific radiotracer targeting dopamine transporter for Parkinson’s diagnosis
LBT
LBT-999 is an analog of tropane, initially developed by Tours University (France). This molecule has a high affinity and an excellent selectivity for the dopamine transporter (DAT). DAT is a protein located in synaptic clefts and is essential to the neurotransmission dynamic. LBT-999 ensures a prompt and efficient recapture of the released dopamine, thus controlling precisely spatially and temporally this neurotransmitter amount.
Labelled with Fluor-18, LBT-999, combined with a PET Scan, allows physicians to visualize and quantify the DAT in striato-nigral nerve endings (caudate nuclei and putamen).
During Parkinson’s disease, the degeneration of dopaminergic fibers reaching the striatum coincide with a decrease, not only of dopamine but also of the DAT. We can then observe a hyposignal of LBT-999 in the striatum. A simple exam combining LBT-999 has the potential to confirm the clinical diagnostic of Parkinson’s disease in a non-invasive way. It also allows physicians to differentiate this neurodegenerative disease from others having the same motor clinical symptomatology as some dementias (Lewy body dementia).
For investigational use only – for more information, please contact medicalaffairs@zionexa.com
Publications
- Malherbe C, Bidault R, Netter C, Guilloteau D, Vercouillie J, Arlicot N. Development of a Fast and Facile Analytical Approach to Quantify Radiometabolites in Human Plasma Samples Using Ultra High Performance Liquid Chromatography. Am J Anal Chem. 2019;10(05):185‑201. (2019)
- Chalon S, Vercouillie J, Payoux P, et al. The Story of the Dopamine Transporter PET Tracer LBT-999: From Conception to Clinical Use. Front Med. 2019, 6, 90. (2019)
- Sérrière S, Doméné A, Vercouillie J, Mothes C, Bodard S, Rodrigues N, et al. Assessment of the Protection of Dopaminergic Neurons by an α7 Nicotinic Receptor Agonist, PHA 543613 Using [18F]LBT-999 in a Parkinson’s Disease Rat Model. Front Med. 2015, 2, 61. (2015)
- Serriere S, Tauber C, Vercouillie J, Guilloteau D, Deloye JB, Garreau L, et al. In vivo PET quantification of the dopamine transporter in rat brain with [18F]LBT-999. Nucl Med Biol 2014;41:106-13. (2015)
- Peyronneau, M.A. Saba, W., Dollé, F., Goutal, S., Coulon, C., Bottlaender, M., Valette, H. Difficulties in dopamine transporter radioligand PET analysis: the example of LBT-999 using [18F] and [11C] labelling: Part II: Metabolism studies. Nucl Med and Biol. 2012, 39, 347-359 (2012)
- Saba, W., Peyronneau, M.A., Dollé, F., Goutal, S., Bottlaender, M., Valette, H. Difficulties in dopamine transporter radioligand PET analysis: the example of LBT-999 using [18F] and [11C] labelling: Part I: PET studies. Nucl Med and Biol. 2012, 39, 227-233 (2012)
- Varrone A, Stepanov V, Nakao R, Toth M, Gulyas B, Emond P, et al. Imaging of the striatal and extrastriatal dopamine transporter with (18)F-LBT-999: quantification, biodistribution, and radiation dosimetry in nonhuman primates. J Nucl Med 2011;52:1313-21 (2011)
- Riss PJ and Roesch F. Efficient microwave-assisted direct radiosynthesis of [18F]PR04.MZ and [18F]LBT999: selective dopamine transporter ligands for quantitative molecular imaging by means of PET. Bioorg Med Chem 2009;17:7630-4 (2009)
- Dolle F, Emond P, Le Gaillard J, Hinnen F, and Helfenbein J. Method of fluorine-18 labelling of tropane derivatives. WO/2008/059349 (2008)
- Dolle F, Helfenbein J, Hinnen F, Mavel S, Mincheva Z, Saba W, et al. One-step radiosynthesis of [18F]LBT-999: a selective radioligand for the visualization of the dopamine transporter with PET. J Label Compd Radiopharm. 2007;50:716-23 (2007)
- Chalon S, Hall H, Saba W, Garreau L, Dolle F, Halldin C, et al. Pharmacological characterization of (E)-N-(4-fluorobut-2-enyl)-2beta-carbomethoxy-3beta-(4′-tolyl)nortropane (LBT-999) as a highly promising fluorinated ligand for the dopamine transporter. J Pharmacol Exp Ther 2006;317:147-52 (2006)
- Dolle F, Hinnen F, Emond P, Mavel S, Mincheva Z, Saba W, et al. Radiosynthesis of [18F]LBT‐999, a selective radioligand for the visualization of the dopamine transporter with PET. J. Label. Compd. Radiopharm. 2006;49: 687-98 (2006)
- Arlicot N, Vercouillie J, Malherbe C, Bidault R, Gissot V, Maia S, et al. PET imaging of Dopamine Transporter with [18F]LBT-999: initial evaluation in healthy volunteers. Q J Nucl Med Mol Imaging 2019, in press.
