title: A 99Tcm-labelled leukotriene B4 receptor antagonist for scintigraphic detection of infection in rabbits.
abstract: In a search for a rapid and accurate imaging agent for scintigraphic detection of infection and inflammation, an LTB4 receptor antagonist, 99Tcm-RP517, which contains the hydrazino nicotinamide moiety, has been developed recently. To study the in vivo behaviour of 99Tcm-RP517, rabbits with Escherichia coli infection were injected intravenously with 99Tcm-RP517. Gamma camera images were obtained and ex vivo bio-distribution was determined at several hours post-injection (p.i.). In a separate set of rabbits the choledochal duct was cannulated to quantitatively monitor the hepatobiliary clearance of the radiopharmaceutical. The receptor binding fraction of the radiolabelled RP517 exceeded 70%. Accumulation of 99Tcm-RP517 in the abscess was visualized as early as 1 h p.i. Due to rapid blood clearance (t1/2 alpha=18+/-0.6 min, t1/2 beta=6.5+/-0.4 h) and high abscess uptake, the abscess-to-muscle ratios increased with time from 7.0+/-2.3 at 1 h p.i. to 44.3+/-4.6 at 20 h p.i. The agent mainly cleared via the hepatobiliary route: 50% of the radiolabel was recovered in the small bowel at 1 h p.i., whereas 85% was found in cecum and sigmoid at 20 h p.i. In conclusion, 99Tcm-RP517 rapidly visualized E. coli abscesses in rabbits. The agent rapidly cleared from the blood, mainly via the hepatobiliary route. High abscess-to-background ratios were achieved. The accumulation in the intestines could limit the applicability of this agent for detecting infectious processes in the abdominal area. The development of a more hydrophilic analogue of 99Tcm-RP517 could improve the clinical applicability of this agent.
authors.affiliation: Department of Nuclear Medicine, University Medical Center Nijmegen, The Netherlands. a.brouwers@nugen.azn.nl
authors.forename: A H
authors.initials: AH
authors.lastname: Brouwers
authors.forename: P
authors.initials: P
authors.lastname: Laverman
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: J A
authors.initials: JA
authors.lastname: Barrett
authors.forename: T D
authors.initials: TD
authors.lastname: Harris
authors.forename: D S
authors.initials: DS
authors.lastname: Edwards
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
mesh_terms: D000208:Acute Disease; D000818:Animals; D001652:Bile Ducts / Q000000981:diagnostic imaging / Q000502:physiology; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging*; D005243:Feces / Q000737:chemistry; D005260:Female; D015902:Gamma Cameras; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; C425527:RP517; D019275:Radiopharmaceuticals; D018102:Receptors, Leukotriene B4