6 Matching Results

Search Results

Advanced search parameters have been applied.

Synthesis ofN-(2-chloro-5-methylthiophenyl)-N'-(3-methyl-thiophenyl)-N'-[3H3]methylguanidine, l brace [3H3]CNS-5161 r brace

Description: The preparation of the title compound, [{sup 3}H{sub 3}]CNS-5161, was accomplished in three steps starting with the production of [{sup 3}H{sub 3}]iodomethane (CT{sub 3}I). The intermediate N-[{sup 3}H{sub 3}]methyl-3-(thiomethylphenyl)cyanamide was prepared in 77% yield by the addition of CT{sub 3}I to 3-(thiomethylphenyl)cyanamide, previously treated with sodium hydride. Reaction of this tritiated intermediate with 2-chloro-5-thiomethylaniline hydrochloride formed the guanidine compound [{sup 3}H{sub 3}]CNS-5161. Purification by HPLC gave the desired labeled product in an overall yield of 9% with greater than 96% radiochemical purity and a final specific activity of 66 Ci mmol{sup -1}.
Date: September 28, 2001
Creator: Gibbs, Andrew R.; Morimoto, Hiromi; VanBrocklin, Henry F.; Williams, Philip G. & Biegon, Anat
Partner: UNT Libraries Government Documents Department

Synthesis of 6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline: Aprospective irreversible EGFR binding probe

Description: Acrylamido-quinazolines substituted at the 6-position bindirreversibly to the intracellular ATP binding domain of the epidermalgrowth factor receptor (EGFR). A general route was developed forpreparing 6-substituted-4-anilinoquinazolines from [18F]fluoroanilinesfor evaluation as EGFR targeting agents with PET. By a cyclizationreaction, 2-[18F]fluoroaniline was reacted withN'-(2-cyano-4-nitrophenyl)-N,N-dimethylimidoformamide to produce6-nitro-4-(2-[18F]fluoroanilino)quinazoline in 27.5 percentdecay-corrected radiochemical yield. Acid mediated tin chloride reductionof the nitro group was achieved in 5 min (80 percent conversion) andsubsequent acylation with acrylic acid gave6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline in 8.5 percentdecay-corrected radiochemical yield, from starting fluoride, in less than2 hours.
Date: March 30, 2004
Creator: Vasdev, Neil; Dorff, Peter N.; Gibbs, Andrew R.; Nandanan,Erathodiyil; Reid, Leanne M.; O'Neil, James P. et al.
Partner: UNT Libraries Government Documents Department

Kinetic analysis of 18F-fluorodihydrorotenone as a deposited myocardial flow tracer: Comparison to thallium-201.

Description: The goal of this investigation was to assess the accuracy of 18F-fluorodihydrorotenone (18F-FDHR) as a new deposited myocardial flow tracer and compare the results to those for 201Tl. Methods. The kinetics of these flow tracers were evaluated in 22 isolated, erythrocyte- and albumin-perfused rabbit hearts over a flow range encountered in patients. The two flow tracers plus a vascular reference tracer (131I-albumin) were introduced as a bolus through a port just above the aortic cannula. Myocardial extraction, retention, washout, and uptake parameters were computed from the venous outflow curves using the multiple indicator dilution technique and spectral analysis. Results. The mean initial extraction fractions of 18F-FDHR (0.85 +- 0.07) and 201Tl (0.87 +- 0.05) were not significantly different, although the initial extraction fraction for 18F-FDHR declined with flow (P < 0.0001), whereas the initial extraction fraction of 201Tl did not. Washout of 201Tl was faster (P < 0.001) and more affected by flow (P < 0.05) than 18F-FDHR washout. Except for initial extraction fraction, 18F-FDHR retention was greater (P < 0.001) and less affected by flow (P < 0.05) than 201Tl retention. Reflecting its superior retention, net uptake of 18F-FDHR was better correlated with flow than 201Tl uptake at both one and fifteen minutes after tracer introduction (P < 0.0001 for both comparisons). Conclusion. The superior correlation of 18F-FDHR uptake with flow indicates that it is a better flow tracer than 201Tl in the isolated rabbit heart. Compared to the other currently available positron-emitting flow tracers (82Rb, 13N-ammonia, and 15O-water), 18F-FDHR has the potential of providing excellent image resolution without the need for an on-site cyclotron.
Date: March 1, 2004
Creator: Marshall, Robert C.; Powers-Risius, Patricia; Reutter, Bryan W.; O'Neil, James P.; La Belle, Michael; Huesman, Ronald H. et al.
Partner: UNT Libraries Government Documents Department

Dialkoxyquinazolines: Screening Epidermal Growth Factor ReceptorTyrosine Kinase Inhibitors for Potential Tumor Imaging Probes

Description: The epidermal growth factor receptor (EGFR), a long-standingdrug development target, is also a desirable target for imaging. Sixteendialkoxyquinazoline analogs, suitable for labeling with positron-emittingisotopes, have been synthesized and evaluated in a battery of in vitroassays to ascertain their chemical and biological properties. Thesecharacteristics provided the basis for the adoption of a selection schemato identify lead molecules for labeling and in vivo evaluation. A newEGFR tyrosine kinase radiometric binding assay revealed that all of thecompounds possessed suitable affinity (IC50 = 0.4 - 51 nM) for the EGFRtyrosine kinase. All of the analogs inhibited ligand-induced EGFRtyrosine phosphorylation (IC50 = 0.8 - 20 nM). The HPLC-estimatedoctanol/water partition coefficients ranged from 2.0-5.5. Four compounds,4-(2'-fluoroanilino)- and 4-(3'-fluoroanilino)-6,7-diethoxyquinazoline aswell as 4-(3'-chloroanilino)- and4-(3'-bromoanilino)-6,7-dimethoxyquinazoline, possess the bestcombination of characteristics that warrant radioisotope labeling andfurther evaluation in tumor-bearing mice.
Date: September 1, 2005
Creator: VanBrocklin, Henry F.; Lim, John K.; Coffing, Stephanie L.; Hom,Darren L.; Negash, Kitaw; Ono, Michele Y. et al.
Partner: UNT Libraries Government Documents Department

A new precursor for the preparation of 6-[18F]-fluoro-L-m-tyrosine (FMT): Efficient synthesis and comparison of radiolabeling

Description: For the electrophilic preparation of 6-[18F]-Fluoro-L-m-tyrosine (FMT), a PET tracer for measuring changes in dopaminergic function in movement disorders, a novel precursor, N-(tert-butoxycarbonyl)-3-(tert-butoxycarbonyloxy)-6-trimethylstannnyl-L-phenylalanine ethyl ester, was synthesized in four steps and 26 percent yield starting from L-m-tyrosine. FMT produced by two methods at two institutions was comparable in decay corrected yield, 25-26 percent, and quality (chemical, enantiomeric, and radiochemical purity and specific activity) as that obtained with the original N-trifluoroacetyl-3-acetyl-6-trimethylstannyl-L-m-tyrosine ethyl ester FMT precursor.
Date: January 9, 2004
Creator: VanBrocklin, Henry F.; Blagoev, Milan; Hoepping, Alexander; O'Neil, James P.; Klose, Manuela; Schubiger, Pius A. et al.
Partner: UNT Libraries Government Documents Department