A 99Tcm-labelled leukotriene B4 receptor antagonist for scintigraphic detection of infection in rabbits

Nucl Med Commun. 2000 Nov;21(11):1043-50. doi: 10.1097/00006231-200011000-00010.

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.

MeSH terms

  • Acute Disease
  • Animals
  • Bile Ducts / diagnostic imaging
  • Bile Ducts / physiology
  • Escherichia coli Infections / diagnostic imaging*
  • Feces / chemistry
  • Female
  • Gamma Cameras
  • Muscle, Skeletal / diagnostic imaging
  • Organotechnetium Compounds* / pharmacokinetics
  • Rabbits
  • Radionuclide Imaging
  • Radiopharmaceuticals* / pharmacokinetics
  • Receptors, Leukotriene B4 / antagonists & inhibitors*
  • Time Factors
  • Tissue Distribution

Substances

  • Organotechnetium Compounds
  • RP517
  • Radiopharmaceuticals
  • Receptors, Leukotriene B4