Scintigraphic imaging of infectious foci with an 111In-LTB4 antagonist is based on in vivo labeling of granulocytes.
Radiolabeled leukotriene B4 (LTB4) antagonist DPC11870 is able to reveal infectious and inflammatory foci in distinct animal models. Because previous studies showed that accumulation of (111)In-DPC11870 in the abscess continued although the tracer had cleared from the circulation, we decided to investigate the pharmacodynamics of (111)In-DPC11870 and determine the mechanism of accumulation of the radiolabeled LTB4 antagonist in the abscess.


METHODS
(111)In-DPC11870 was intravenously injected in healthy New Zealand White rabbits and rabbits with intramuscular Escherichia coli infection. Pharmacodynamics were studied by serial imaging and by ex vivo counting of dissected tissues. The mechanism of visualization of the abscess was investigated in rabbits with intramuscular infection that was induced 16 h after intravenous administration of (111)In-DPC11870. In addition, heterologous leukocytes and bone marrow cells of a donor rabbit were labeled with (111)In-DPC11870 in vitro and the biodistribution of these in vitro radiolabeled cells was compared with that of (111)In-DPC11870 in rabbits with an infection.


RESULTS
The LTB4 antagonist (111)In-DPC11870 revealed the intramuscular abscess in rabbits only a few hours after injection. Quantitative analysis of the images confirmed accumulation of (111)In-DPC11870 in the abscess although the compound had cleared almost completely from the circulation. Radioactivity concentration in the bone marrow decreased more rapidly in infected animals than in healthy animals. Therefore, we hypothesized that (111)In-DPC11870 associates with receptor-positive (bone marrow) cells and accumulated in the abscess because of subsequent migration from the bone marrow to the abscess. Accumulation of radioactivity in the abscess induced 16 h after (111)In-DPC11870 injection was similar to that in animals intravenously injected with the tracer 24 h after induction of the abscess (0.37 +/- 0.16 percentage injected dose [%ID]/g). Moreover, differences in radioactivity concentration in the bone marrow of healthy and infected animals (0.67 +/- 0.29 %ID/g and 0.15 +/- 0.03 %ID/g at 24 h, respectively, after injection) supported our hypothesis. Additional studies with peripheral blood leukocytes and bone marrow cells that were labeled ex vivo with (111)In-DPC11870 showed the ability of these cells to migrate to the abscess (0.40 %ID/g and 0.52 %ID/g for (111)In-DPC11870 bone marrow cells and (111)In-DPC11870 peripheral blood leukocytes, respectively, 24 h after injection).


CONCLUSIONS
The (111)In-labeled LTB4 antagonist DPC11870 accumulates in infectious and inflammatory foci because of binding to LTB4 receptors expressed on activated hematopoietic cells that subsequently migrate to the site of infection, which leads to visualization of the infectious lesions.
van Eerd
Julliëtte E M
JE
Department of Nuclear Medicine, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. J.vaneerd@nucmed.umcn.nl
Oyen
Wim J G
WJ
Harris
Thomas D
TD
Rennen
Huub J J M
HJ
Edwards
D Scott
DS
Corstens
Frans H M
FH
Boerman
Otto C
OC
D000818:Animals; D001713:Biphenyl Compounds / Q000493:pharmacokinetics*; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006098:Granulocytes / Q000000981:diagnostic imaging*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D008657:Metabolic Clearance Rate; D009842:Oligopeptides / Q000493:pharmacokinetics*; D009928:Organ Specificity; D011725:Pyridines / Q000493:pharmacokinetics*; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013777:Tetrazoles / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014915:Whole-Body Counting
D001713:Biphenyl Compounds; C476701:DPC11870-11; D009842:Oligopeptides; D011725:Pyridines; D019275:Radiopharmaceuticals; D013777:Tetrazoles; D007975:Leukotriene B4