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Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3 Receptors.

van Wieringen JP, de Bruin K, Janssen HM, Fransen PM, Janssen AG, van Doremalen PA, Michel MC, Elsinga PH, Booij J - Int J Mol Imaging (2014)

Bottom Line: The appropriate tin precursor for [(123)I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30-35%) and a good purity (>95%) for [(123)I]-1.In biodistribution experiments in Wistar rats intravenous injection of [(123)I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i.In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [(123)I]-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.

ABSTRACT
For imaging of dopamine D2/3 receptors, agonist tracers are favoured over antagonists because they are more sensitive to detection of dopamine release and because they may selectively label the high-affinity receptor state. We have developed novel D2/3 receptor selective agonists that can be radiolabelled with [(123)I], which label is advantageous over most other labels, such as carbon-11, as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman-2-yl]-methyl 4-iodobenzyl amine (compound 1) as an attractive candidate for development as it shows high binding affinity to D2/3 receptors in vitro, and here we report on the characterization of this first [(123)I]-labelled D2/3 receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate tin precursor for [(123)I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30-35%) and a good purity (>95%) for [(123)I]-1. In biodistribution experiments in Wistar rats intravenous injection of [(123)I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i. Storage phosphor imaging experiments, however, did not show specific D2/3 receptor binding. In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [(123)I]-1.

No MeSH data available.


Results of biodistribution studies in Wistar rats. Uptake ratios of uptake in several brain areas compared to cerebellum uptake at different times after intravenous injection of [123I]-1.
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fig1: Results of biodistribution studies in Wistar rats. Uptake ratios of uptake in several brain areas compared to cerebellum uptake at different times after intravenous injection of [123I]-1.

Mentions: The biodistribution studies showed that the uptake of [123I]-1 was higher in all brain areas than in blood from 15 min up to 1 h postinjection (p.i.) (Table 1 and Figure 1), suggesting efficient passage of the radiopharmaceutical through the blood-brain barrier. In almost all brain areas, [123I]-1 uptake was higher than in the cerebellum (Tables 1 and 2) from 15 min to 24 h p.i. As can be seen in Table 2 and Figure 1, the mean ratio of striatum/cerebellum binding was about 1.3 and was stable for the period of 30 min to 4 h p.i. In addition, the variation in binding was low in this period; therefore 2 h p.i. was chosen as time point to sacrifice the rats during the subsequent storage phosphor imaging experiment (see Tables 1 and 2 and Figure 1). Uptake in the pituitary, another part of the brain with a relatively high density of dopamine D2 receptor, was also relatively high.


Ex Vivo Characterization of a Novel Iodine-123-Labelled Aminomethylchroman as a Potential Agonist Ligand for SPECT Imaging of Dopamine D2/3 Receptors.

van Wieringen JP, de Bruin K, Janssen HM, Fransen PM, Janssen AG, van Doremalen PA, Michel MC, Elsinga PH, Booij J - Int J Mol Imaging (2014)

Results of biodistribution studies in Wistar rats. Uptake ratios of uptake in several brain areas compared to cerebellum uptake at different times after intravenous injection of [123I]-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4291083&req=5

fig1: Results of biodistribution studies in Wistar rats. Uptake ratios of uptake in several brain areas compared to cerebellum uptake at different times after intravenous injection of [123I]-1.
Mentions: The biodistribution studies showed that the uptake of [123I]-1 was higher in all brain areas than in blood from 15 min up to 1 h postinjection (p.i.) (Table 1 and Figure 1), suggesting efficient passage of the radiopharmaceutical through the blood-brain barrier. In almost all brain areas, [123I]-1 uptake was higher than in the cerebellum (Tables 1 and 2) from 15 min to 24 h p.i. As can be seen in Table 2 and Figure 1, the mean ratio of striatum/cerebellum binding was about 1.3 and was stable for the period of 30 min to 4 h p.i. In addition, the variation in binding was low in this period; therefore 2 h p.i. was chosen as time point to sacrifice the rats during the subsequent storage phosphor imaging experiment (see Tables 1 and 2 and Figure 1). Uptake in the pituitary, another part of the brain with a relatively high density of dopamine D2 receptor, was also relatively high.

Bottom Line: The appropriate tin precursor for [(123)I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30-35%) and a good purity (>95%) for [(123)I]-1.In biodistribution experiments in Wistar rats intravenous injection of [(123)I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i.In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [(123)I]-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.

ABSTRACT
For imaging of dopamine D2/3 receptors, agonist tracers are favoured over antagonists because they are more sensitive to detection of dopamine release and because they may selectively label the high-affinity receptor state. We have developed novel D2/3 receptor selective agonists that can be radiolabelled with [(123)I], which label is advantageous over most other labels, such as carbon-11, as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman-2-yl]-methyl 4-iodobenzyl amine (compound 1) as an attractive candidate for development as it shows high binding affinity to D2/3 receptors in vitro, and here we report on the characterization of this first [(123)I]-labelled D2/3 receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate tin precursor for [(123)I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30-35%) and a good purity (>95%) for [(123)I]-1. In biodistribution experiments in Wistar rats intravenous injection of [(123)I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i. Storage phosphor imaging experiments, however, did not show specific D2/3 receptor binding. In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [(123)I]-1.

No MeSH data available.