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Synthesis of leukotriene B4 antagonists labeled with In-111 or Tc-99m to image infectious and inflammatory foci.

Abstract：

:In previous studies we demonstrated that lipophilic (99m)Tc-labeled LTB4 antagonist 1 (RP517) accumulated in infectious foci in rabbits, but hepatobiliary clearance hampered imaging of abdominal lesions. We now report the use of cysteic acid as a pharmacokinetic modifier to improve the water solubility and renal clearance of three hydrophilic analogues of 1. Divalent LTB4 antagonist 17 (DPC11870-11) is a DTPA conjugate for radiolabeling with In-111. Monovalent LTB4 antagonists 15 (BMS57868-88) and divalent LTB4 antagonist 18 (BMS57868-81) are conjugated to bifunctional chelator HYNIC for radiolabeling with (99m)Tc. The three compounds labeled efficiently with 111In or (99m)Tc with high radiochemical purity and specific activities. Scintigraphic images obtained in New Zealand White rabbits having acute intramuscular E. coli infection demonstrated that all agents were able to clearly visualize the abscess, and clearance was exclusively renal. The biodistribution of the (99m)Tc-labeled LTB4 antagonists was affected by the coligands used with the HYNIC chelator and by the monovalent or divalent nature of the receptor binding moiety. The best scintigraphic images were obtained with monovalent HYNIC conjugate 15 using tricine and isonicotinic acid as coligands with HYNIC for coordination with (99m)Tc.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Broekema M,van Eerd JJ,Oyen WJ,Corstens FH,Liskamp RM,Boerman OC,Harris TD

doi

10.1021/jm050383h

keywords:

subject

Has Abstract

pub_date

2005-10-06 00:00:00

pages

6442-53

issue

20

eissn

0022-2623

issn

1520-4804

journal_volume

48

pub_type

杂志文章

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