Doerner, Bernd; Kuntner, Claudia; Bankstahl, Jens P.; Wanek, Thomas; Bankstahl, Marion; Stanek, Johann; Muellauer, Julia; Bauer, Florian; Mairinger, Severin; Loescher, Wolfgang; Miller, Donald W.; Chiba, Peter; Mueller, Markus; Erker, Thomas; Langer, Oliver published the artcile< Radiosynthesis and in vivo evaluation of 1-[18F]fluoroelacridar as a positron emission tomography tracer for P-glycoprotein and breast cancer resistance protein>, COA of Formula: C7H4BrNO4, the main research area is fluorine 18 elacridar preparation PET tumor imaging Pgp BCRP.
Aim of this study was to label the potent dual P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) inhibitor elacridar (1) with 18F to provide a positron emission tomog. (PET) radiotracer to visualize Pgp and BCRP. A series of new 1- and 2-halogen- and nitro-substituted derivatives of 1 (4a-e) was synthesized as precursor mols. and reference compounds for radiolabelling and shown to display comparable in vitro potency to 1 in increasing rhodamine 123 accumulation in a cell line overexpressing human Pgp (MDCKII-MDR1). 1-[18F]fluoroelacridar ([18F]4b) was synthesized in a decay-corrected radiochem. yield of 1.7 ± 0.9% by a 1-step no-carrier added nucleophilic aromatic 18F-substitution of 1-nitro precursor 4c. Small-animal PET imaging of [18F]4b was performed in naive rats, before and after administration of unlabeled 1 (5 mg/kg, n = 3), as well as in wild-type and Mdr1a/b (-/-) Bcrp1 (-/-) mice (n = 3). In PET experiments in rats, administration of unlabeled 1 increased brain activity uptake by a factor of 9.5 (p = 0.0002, 2-tailed Student’s t-test), whereas blood activity levels remained unchanged. In Mdr1a/b (-/-) Bcrp1 (-/-) mice, the mean brain-to-blood ratio of activity at 60 min after tracer injection was 7.6 times higher as compared to wild-type animals (p = 0.0002). HPLC anal. of rat brain tissue extracts collected at 40 min after injection of [18F]4b revealed that 93 ± 7% of total radioactivity in brain was in the form of unchanged [18F]4b. In conclusion, the in vivo behavior of [18F]4b was found to be similar to previously described [11C]1 suggesting transport of [18F]4b by Pgp and/or BCRP at the rodent BBB. However, low radiochem. yields and a significant degree of in vivo defluorination will limit the utility of [18F]4b as a PET tracer.
Bioorganic & Medicinal Chemistry published new progress about Animal gene, MDR1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 16426-64-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H4BrNO4, COA of Formula: C7H4BrNO4.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary