Document Detail


Preparation and characterization of [99TcO] apcitide: a technetium labeled peptide.
MedLine Citation:
PMID:  15106974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
[99mTcO] apcitide (99mTcO(P246)), the technetium complex of the 13 amino acid, apcitide, cyclo-(D-Tyr-Apc-Gly-Asp-Cys)-Gly-Gly-Cys(Acm)-Gly-Cys(Acm)-Gly-Gly-Cys-NH2, where Apc is L-[S-(3-aminopropyl)]cysteine (an arginine mimetic) and Acm is the acetamidomethyl protecting group, has high affinity and selectivity for the GPIIb/IIIa receptor that is expressed on the membrane surface of activated platelets and plays an integral role in platelet aggregation and thrombus formation. Bibapcitide, a 26 amino acid, bis-succinimidomethyl ether-linked dimer of the peptide apcitide has been formulated as a single-vial, lyophilized kit having the trade name AcuTect. When sterile, nonpyrogenic sodium pertechnetate (99mTcO4-) in 0.9% sodium chloride is added to the AcuTect radiopharmaceutical kit and the resulting kit is heated, [99mTcO] apcitide forms. This is the first radiopharmaceutical to target acute deep vein thrombosis (DVT) in the lower extremities. We report here the preparation, purification, and isolation of the 99Tc complex of apcitide and its characterization to determine the mode of binding of Tc to apcitide. [99TcO] apcitide was prepared, on the macroscopic level, by reaction of [99TcOCl4]- with apcitide, purified by preparative HPLC and isolated as a trifluoroacetate salt. [99TcO] apcitide can also be formed from the reaction of bibapcitide and 99TcO4- in the presence of Sn(II) and glucoheptonate at 80 degrees C, conditions that mimic the radiopharmaceutical kit preparation. FTIR data show a Tc=O stretch at 961.2 cm(-1), in the range observed for anionic [TcVO]3+ amide thiolate complexes. The mass spectral data is in agreement with the formula, [C51H73O20N17S5Tc]-, consistent with retention of Acm groups and the Tc binding in the Gly11-Gly12-Cys13 region of the peptide. Despite significant spectral overlap due to numerous similar amino acids, all protons of apcitide and [99TcO] apcitide were unambiguously assigned. The observation of two nonequivalent Acm groups and the observation of only 10 NH-CH cross-peaks in the TOCSY and COSY spectra of [99TcO] apcitide (NH-CH cross-peaks were absent for Gly11-Gly12-Cys13), compared to all 13 cross-peaks found in apcitide, provided compelling evidence to support the 99Tc binding to the terminal Gly11-Gly12-Cys13 region of apcitide.
Authors:
Lynn C Francesconi; Yongyong Zheng; Judit Bartis; Michael Blumenstein; Catherine Costello; Mark A De Rosch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Inorganic chemistry     Volume:  43     ISSN:  0020-1669     ISO Abbreviation:  Inorg Chem     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-26     Completed Date:  2004-06-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0366543     Medline TA:  Inorg Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2867-75     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Hunter College and the Graduate School of the City University of New York, New York, New York 10021, USA. lfrances@hunter.cuny.edu
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Chromatography, High Pressure Liquid
Crystallography, X-Ray
Magnetic Resonance Spectroscopy
Molecular Structure
Oligopeptides / chemistry*
Organotechnetium Compounds / chemical synthesis*,  chemistry*
Peptides / chemistry*
Peptides, Cyclic / chemical synthesis*,  chemistry*
Radiopharmaceuticals / chemistry*
Grant Support
ID/Acronym/Agency:
RR03037-08S2/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Oligopeptides; 0/Organotechnetium Compounds; 0/Peptides; 0/Peptides, Cyclic; 0/Radiopharmaceuticals; 0/technetium Tc 99m P280; 95416-30-1/glycyl-glycyl-cysteine

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