Petrogenesis and Geodynamic Implications of Miocene Felsic Magmatic Rocks in the Wuyu Basin, Southern Gangdese Belt, Qinghai-Tibet Plateau

Miocene felsic magmatic rocks with high Sr/Y ratios are widely distributed throughout the Gangdese belt of southern Tibet. These provide a good opportunity to explore the magmatic process and deep dynamic mechanisms that occurred after collision between the Indo and the Asian plates. In this paper, felsic volcanic rocks from the Zongdangcun Formation in the Wuyu Basin in the central part of the southern Gangdese belt are used to disclose their origin. Zircon U-Pb geochronology analysis shows that the felsic magmatism occurred at ca. 10.3 ± 0.2 Ma, indicating that the Zongdangcun Formation formed during the Miocene. Most of these felsic magmatic rocks plot in the rhyolite area in the TAS diagram. The rhyolite specimens from the Zongdangcun Formation have the characteristics of high SiO2 (>64%), K2O, SiO2, and Sr contents, a low Y content and a high Sr/Y ratio, and the rocks are rich in LREE and depleted in HREE, showing geochemical affinity to adakitic rocks. The rocks have an enriched Sr-Nd isotopic composition (εNd(t) = −6.76 to −6.68, (87Sr/86Sr)i = 0.7082–0.7088), which is similar to the mixed product of the juvenile Lhasa lower continental crust and the ancient Indian crust. The Hf isotopes of zircon define a wide compositional range (εHf(t) = −4.19 to 6.72) with predominant enriched signatures. The Miocene-aged crustal thickness in southern Tibet, calculated on the basis of the Sr/Y and (La/Yb)N ratios was approximately 60–80 km, which is consistent with the thickening of the Qinghai-Tibet Plateau. The origin of Miocene felsic magmatic rocks with high Sr/Y ratios in the middle section of the Gangdese belt likely involved a partial melting of the thickened lower crust, essentially formed by the lower crust of the Lhasa block, with minor contribution from the ancient Indian crust. After comprehensively analyzing the post-collisional high Sr/Y magmatic rocks (33–8 Ma) collected from the southern margin of the Gangdese belt, we propose that the front edge tearing and segmented subduction of the Indian continental slab may be the major factor driving the east-west trending compositional changes of the Miocene adakitic rocks in southern Tibet

Synthesis and preliminary evaluation of 18F-labeled 1-(6,7-dimethyl-4-(methylamino)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-2-(trans-2-(6-fluoropyridin-3-yl)cyclopropyl)ethan-1-one for imaging muscarinic acetylcholine receptor subtype 4

Positive allosteric modulators of muscarinic acetylcholine receptor subtype 4 have been identified as promising activators for the treatment of neurological disorders and neurodegenerative diseases, including schizophrenia, Alzheimer\u27s disease (AD) and dementia with Lewy bodies (DLB). Herein we report the synthesis and preliminary evaluation of a 18F-labeled positron emission tomography ligand based on a M4 activator (7). 18F-Isotopologue of 7 was prepared in a reasonable radiochemical yield with high radiochemical purity (>99%) and high molar activity (>37 GBq/µmol). In vitro autoradiography studies indicated that the ligand possessed moderate in vitro specific binding. Dynamic PET studies in vivo demonstrated that [18F]7 (also named as [18F]M4R-1911) failed to cross the blood–brain barrier. Therefore, further chemical scaffold optimization in chemotype of 7 is necessary to overcome limited brain permeability and improve specific binding

Synthesis and Preliminary Evaluation of C-11-Labeled VU0467485/AZ13713945 and Its Analogues for Imaging Muscarinic Acetylcholine Receptor Subtype 4

Muscarinic acetylcholine receptors (mAChRs) have five distinct subunits (M1–M5) and are involved in the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. Attributed to the promising clinical efficacy of xanomeline, an M1/M4‐preferring agonist, in patients of schizophrenia and Alzheimer\u27s disease, M1‐ or M4‐selective mAChR modulators have been developed that target the topographically distinct allosteric sites. Herein we report the synthesis and preliminary evaluation of 11C‐labeled positron emission tomography (PET) ligands based on a validated M4R positive allosteric modulator VU0467485 (AZ13713945) to facilitate drug discovery. [11C]VU0467485 and two other ligands were prepared in high radiochemical yields (>30 %, decay‐corrected) with high radiochemical purity (>99 %) and high molar activity (>74 GBq μmol−1). In vitro autoradiography studies indicated that these three ligands possess moderate‐to‐high in vitro specific binding to M4R. Nevertheless, further physiochemical property optimization is necessary to overcome the challenges associated with limited brain permeability