TY - JOUR T1 - Scintigraphic Imaging of Infectious Foci with an <sup>111</sup>In-LTB4 Antagonist Is Based on In Vivo Labeling of Granulocytes JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 786 LP - 793 VL - 46 IS - 5 AU - Julliëtte E.M. van Eerd AU - Wim J.G. Oyen AU - Thomas D. Harris AU - Huub J.J.M. Rennen AU - D. Scott Edwards AU - Frans H.M. Corstens AU - Otto C. Boerman Y1 - 2005/05/01 UR - http://jnm.snmjournals.org/content/46/5/786.abstract N2 - 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 111In-DPC11870 in the abscess continued although the tracer had cleared from the circulation, we decided to investigate the pharmacodynamics of 111In-DPC11870 and determine the mechanism of accumulation of the radiolabeled LTB4 antagonist in the abscess. Methods: 111In-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 111In-DPC11870. In addition, heterologous leukocytes and bone marrow cells of a donor rabbit were labeled with 111In-DPC11870 in vitro and the biodistribution of these in vitro radiolabeled cells was compared with that of 111In-DPC11870 in rabbits with an infection. Results: The LTB4 antagonist 111In-DPC11870 revealed the intramuscular abscess in rabbits only a few hours after injection. Quantitative analysis of the images confirmed accumulation of 111In-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 111In-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 111In-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 111In-DPC11870 showed the ability of these cells to migrate to the abscess (0.40 %ID/g and 0.52 %ID/g for 111In-DPC11870 bone marrow cells and 111In-DPC11870 peripheral blood leukocytes, respectively, 24 h after injection). Conclusion: The 111In-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. ER -