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Targeting Metal-Aβ Aggregates with Bifunctional Radioligand [ 11 C]L2-b and a Fluorine-18 Analogue [ 18 F]FL2-b.
- Source :
-
ACS medicinal chemistry letters [ACS Med Chem Lett] 2014 Nov 09; Vol. 6 (2), pp. 112-116. Date of Electronic Publication: 2014 Nov 09 (Print Publication: 2015). - Publication Year :
- 2014
-
Abstract
- Interest in quantifying metal-Aβ species in vivo led to the synthesis and evaluation of [ <superscript>11</superscript> C]L2-b and [ <superscript>18</superscript> F]FL2-b as radiopharmaceuticals for studying the metallobiology of Alzheimer's disease (AD) using positron emission tomography (PET) imaging. [ <superscript>11</superscript> C]L2-b was synthesized in 3.6% radiochemical yield (nondecay corrected, n = 3), >95% radiochemical purity, from the corresponding desmethyl precursor. [ <superscript>18</superscript> F]FL2-b was synthesized in 1.0% radiochemical yield (nondecay corrected, n = 3), >99% radiochemical purity, from a 6-chloro pyridine precursor. Autoradiography experiments with AD positive and healthy control brain samples were used to determine the specificity of binding for the radioligands compared to [ <superscript>11</superscript> C]PiB, a known imaging agent for β-amyloid (Aβ) aggregates. The K <subscript>d</subscript> for [ <superscript>11</superscript> C]L2-b and [ <superscript>18</superscript> F]FL2-b were found to be 3.5 and 9.4 nM, respectively, from those tissue studies. Displacement studies of [ <superscript>11</superscript> C]L2-b and [ <superscript>18</superscript> F]FL2-b with PiB and AV-45 determined that L2-b binds to Aβ aggregates differently from known radiopharmaceuticals. Finally, brain uptake of [ <superscript>11</superscript> C]L2-b was examined through microPET imaging in healthy rhesus macaque, which revealed a maximum uptake at 2.5 min (peak SUV = 2.0) followed by rapid egress ( n = 2).
Details
- Language :
- English
- ISSN :
- 1948-5875
- Volume :
- 6
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- ACS medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 25705326
- Full Text :
- https://doi.org/10.1021/ml500413d