99mTc-labeled interleukin-8 for scintigraphic detection of pulmonary infections.
BACKGROUND
Interleukin (IL)-8 is a chemotactic cytokine that binds with high affinity to receptors on neutrophils. Previously we showed that (99m)Tc-labeled IL-8 is highly suitable for scintigraphic imaging in rabbit models of IM infection and of colitis.


METHODS
(99m)Tc-labeled IL-8 was tested for its potential to image pulmonary infection in three experimental rabbit models: aspergillosis in immunocompromised rabbits, pneumococcal (Gram-positive) pneumonia, and Escherichia coli-induced (Gram-negative) pneumonia in immunocompetent rabbits (four rabbits in each group). A derivative of hydrazinonicotinamide was used as bifunctional coupling agent to label IL-8 with (99m)Tc. Biodistribution of (99m)Tc IL-8 was determined both by gamma-camera imaging and by counting dissected tissues at 6 h after injection.


RESULTS
(99m)Tc IL-8 enabled early (within 2 h after injection) and excellent visualization of localization and extent of pulmonary infection in each of the three experimental models of pulmonary infection. Uptake of (99m)Tc IL-8 in the infected lung and the contralateral lung was (in percentage of the injected dose per gram of tissue +/- SEM) at 6 h after injection 0.63 +/- 0.12 and 0.12 +/- 0.02 (aspergillosis), 0.89 +/- 0.04 and 0.44 +/- 0.04 (pneumococcal pneumonia), and 1.53 +/- 0.12 and 0.36 +/- 0.06 (E coli pneumonia), respectively. In the E coli model, uptake of (99m)Tc IL-8 in the focus of infection even exceeded uptake in the kidneys, the main clearing organs.


CONCLUSIONS
(99m)Tc IL-8 offers many advantages over the conventionally used radiopharmaceuticals to image pulmonary infection, (67)Ga citrate and radiolabeled leukocytes, ie, rapid and easy preparation, short time span between injection and imaging, low radiation burden and, most importantly, clear delineation of the infectious foci.
Rennen
Huub J J M
HJ
Department of Nuclear Medicine, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands. H.Rennen@nucmed.umcn.nl
Bleeker-Rovers
Chantal P
CP
van Eerd
Julliëtte E M
JE
Frielink
Cathelijne
C
Oyen
Wim J G
WJ
Corstens
Frans H M
FH
Boerman
Otto C
OC
D000818:Animals; D001228:Aspergillosis / Q000000981:diagnostic imaging* / Q000276:immunology; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging; D016867:Immunocompromised Host; D016209:Interleukin-8; D008168:Lung / Q000000981:diagnostic imaging; D008172:Lung Diseases, Fungal / Q000000981:diagnostic imaging* / Q000276:immunology; D015609:Organotechnetium Compounds; D018410:Pneumonia, Bacterial / Q000000981:diagnostic imaging*; D011018:Pneumonia, Pneumococcal / Q000000981:diagnostic imaging; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals
D016209:Interleukin-8; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C433789:technetium Tc 99m interleukin 8