588692-07-3Relevant articles and documents
Synthesis and Biological Evaluation of Polar Functionalities Containing Nitrodihydroimidazooxazoles as Anti-TB Agents
Yempalla, Kushalava Reddy,Munagala, Gurunadham,Singh, Samsher,Kour, Gurleen,Sharma, Shweta,Chib, Reena,Kumar, Sunil,Wazir, Priya,Singh,Raina, Sushil,Bharate, Sonali S,Khan, Inshad Ali,Vishwakarma, Ram A.,Singh, Parvinder Pal
, p. 1059 - 1064 (2015)
Novel polar functionalities containing 6-nitro-2,3-dihydroimidazooxazole (NHIO) analogues were synthesized to produce a compound with enhanced solubility. Polar functionalities including sulfonyl, uridyl, and thiouridyl-bearing NHIO analogues were synthes
IMAGING TUMOR GLYCOLYSIS BY NON-INVASIVE MEASUREMENT OF PYRUVATE KINASE M2
-
Paragraph 0138, (2018/03/25)
The present disclosure provides a positron emission tomography (PET)-detectable 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) probe that can selectively bind to the pyruvate kinase variant M2 (PKM2) found in cancer cells, such as of human glioma. Given the importance of PKM2 in the regulation of tumor metabolism, there is an on-going need to non-invasively measure its expression through the development of PKM2-specific radiopharmaceuticals. Precursors useful for the synthesis of the radiolabeled [18F]DASA-23-PKM2-specific probe and related compounds, and their methods of synthesis, are provided. Since the half-life of the 18F isotope is approximately 110 min, it is advantageous for a practitioner to attach the radionuclide to the precursor shortly before administration. Therefore, a precursor compound suitable for receiving the radionuclide and capable of specifically binding to the PKM2 variant can be provided.
Development of [18F]DASA-23 for Imaging Tumor Glycolysis Through Noninvasive Measurement of Pyruvate Kinase M2
Beinat, Corinne,Alam, Israt S.,James, Michelle L.,Srinivasan, Ananth,Gambhir, Sanjiv Sam
, p. 665 - 672 (2017/09/05)
Purpose: A hallmark of cancer is metabolic reprogramming, which is exploited by cancer cells to ensure rapid growth and survival. Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key step in tumor metabolism and growth. Recently, we reported the radiosynthesis of the first positron emission tomography tracer for visualizing PKM2 in vivo—i.e., [11C]DASA-23. Due to the highly promising imaging results obtained with [11C]DASA-23 in rodent model glioblastoma, we set out to generate an F-18-labeled version of this tracer, with the end goal of clinical translation in mind. Herein, we report the radiosynthesis of 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) and our initial investigation of its binding properties in cancer cells. Procedure: We synthesized [18F]DASA-23 via fluorination of 1-((2-fluoro-6-nitrophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine (10) with K[18F]F/K2.2.2 in N,N-dimethylformamide at 110?°C for 20?min. Subsequently, we evaluated uptake of [18F]DASA-23 in HeLa cervical adenocarcinoma cells and in vitro stability in human and mouse serum. Results: We successfully prepared [18F]DASA-23 in 2.61?±?1.54?% radiochemical yield (n?=?10, non-decay corrected at end of synthesis) with a specific activity of 2.59?±?0.44?Ci/μmol. Preliminary cell uptake experiments revealed high uptake in HeLa cells, which was effectively blocked by pretreating cells with the structurally distinct PKM2 activator, TEPP-46. [18F]DASA-23 remained intact in human and mouse serum up to 120?min. Conclusion: Herein, we have identified a F-18-labeled PKM2 specific radiotracer which shows potential for in vivo imaging. The promising cell uptake results reported herein warrant the further evaluation of [18F]DASA-23 for its ability to detect and monitor cancer noninvasively.
