Tc-99m-labeled fibrinogen receptor antagonists: Design and synthesis of cyclic RGD peptides for the detection of thrombi

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 15, 1996, Pages 1741-1746

  Harris, Thomas D ^a   Rajopadhye, Milind ^a   Damphousse, Paul R ^a   Glowacka, Danuta ^a   Yu, Karmine ^a   Bourque, Jeffrey P ^a   Barrett, John A ^a   Damphousse, David J ^a   Heminway, Stuart J ^a   Lazewatsky, Joel ^a   Mazaika, Theresa ^a   Carroll, Timothy R ^a  

^a DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHELATING AGENT; CYCLOPEPTIDE; FIBRINOGEN RECEPTOR ANTAGONIST; IODINE 125; TECHNETIUM 99M;

ANIMAL MODEL; ARTICLE; CHELATION; CONTROLLED STUDY; DOG; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; DRUG UPTAKE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; INTRAVENOUS DRUG ADMINISTRATION; ISOTOPE LABELING; NONHUMAN; THROMBOSIS; THROMBUS;

ANIMALIA; CANIS FAMILIARIS; THROMBUS;

EID: 0030572477     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00282-X     Document Type: Article

References (26)

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8. 5. For a similar strategy see: Pearson, D. A.; Lister-James, J.; McBride, W.; Wilson, D. M.; Martel, J.; Civitello, E. R.; Dean, R. T. J. Med. Chem. 1996, 39, 1372.
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11. 18 column (4.6 mm x 25 cm) at a flow rate of 1.0 mL/min.; a gradient mobile phase from 98% A (0.1% TFA in water) to 100% B (0.1% TFA in 90% acetonitrile) at 45 min was used. UV detection was set at 220 nm. Purity was greater than 95% (% peak area). HRMS for the peptides was consistent with theoretical calculations.
12. 8. (a) DeGrado, W. F; Mousa, S. A.; Sworin, M.; Barrett, J. A.; Edwards, D. S.; Harris, T. D.; Rajopadhye, M.; Liu, S.; WO 9422494 A1; MARPAT 123:199405; CAPLUS 1995:767392.
13. (b) Peptide 1 was provided by Sharon Jackson and William DeGrado, DuPont Merck.
14. 13a
15. (b) Liu, S.; Edwards, D. S.; Looby, R. J.; Poirier, M. J.; Rajopadhye, M.; Bourque, J. P.; Carroll, T. R. Bioconj. Chem. 1996, 7, 196.
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18. 10. (a) Presented at the 1994 Society of Nuclear Medicine meeting. Harris, T. D.; Barrett, J. A.; Bourque, J. P.; Carroll, T. R.; Damphousse, P. R.; Edwards, D. S.; Glowacka, D.; Liu, S.; Looby, R. J.; Poirier, M. J.; Rajopadhye, M.; Yu, K. J. Nucl. Med. 1994, 35, 245P.
19. (b) 4.6 x 250 mm Vydac C18 column, 1.0 mL/min flow rate, linear gradient from 0% B to 30% B at 15 min to 75% B at 25 min. Solvent A = 10 mM phosphate, pH 6, Solvent B = acetonitrile.
20. 11. Iodination (I-125) of 1 and 4 were performed by DuPont Medical Products, Boston.
21. 12. O'Neil, J. P.; Wilson, S. R.; Katzenellenbogen, J. A. Inorg. Chem. 1994, 33, 319.
22. 13. For Tc-labeling of AADT systems see also: (a) Mahmood, A.; Wolff, J. A.; Davison, A.; Jones, A. G. in Technetium and Rhenium in Chemistry and Nuclear Medicine; Nicolini, M.; Bandoli, G.; Mazzi, U. Eds.; SGE ditoriali: Padova, 1995; pp 211-214.
23. (b) Kung, H. F.; Bradshaw, J. E.; Chumpradit, S.; Zuang, Z. P.; Kung, M. P.; Mu, M.; Frederick, D. Ibid., 1995; pp 293-298.
24. 14. Both femoral arteries and femoral veins of anesthetized adult beagle dogs were cannulated with silicon treated (Sigmacote®), saline filled polyethylene tubing to form extra corporeal arteriovenous shunts (A-V). An occlusive thrombus was formed by the introduction of a thrombogenic surface (4-0 braided silk thread, 5 cm) into one shunt with the other serving as a control. A 1 h shunt period was employed with the test agent administered intravenously as an infusion over 5 min beginning 5 min before insertion of the thrombogenic surface. At the end of the 1 h shunt period the silk was removed, weighed and the uptake (% ID/g) determined via well counting. The thrombus consisted of a platelet rich head on the thrombogenic surface (arterial conditions) and a fibrin rich tail (venous conditions). These were separated and individually counted (see table).
25. 15. (a) Barrett, J.; Edwards, D. S.; Harris, T.; Rajopadhye, M.; Lazewatsky, J.; Liu, S.; Damphousse, D.; Heminway, S.; Mazaika, T.; Thomas, J.; Carroll, T.; Smith, J. Ibid., 1995; pp 275-280.
26. (b) For a detailed description of the thrombus models, see Barrett, J. A.; Damphousse, D. J.; Heminway, S. J.; Liu, S.; Edwards, D. S.; Looby, R. J.; Carroll, T. R. Bioconj. Chem. 1996, 7, 203.