Scintigraphy of acute inflammatory lesions in rats with radiolabelled recombinant human interleukin-8.
We compared 125I-labelled recombinant human interleukin-8 (125I-IL-8) with 111In-labelled human leukocytes (111In-WBC) and 67Ga-citrate for scintigraphic depiction of acute sterile inflammatory lesions in rats. Radioiodination of IL-8 was catalysed by chloramine-T, and human leukocytes were radiolabelled with 111In-oxine. Inflammatory lesions were induced in male rats by subcutaneous injection of 2% carrageenan suspension into their left hindlimbs. Twenty-four hours later, each rat received 1.8-3.7 MBq (50-100 microCi) of a single agent by intravenous injection. Sequential whole-body scintigrams were obtained between 0 and 96 h post-injection. Activities in the lesion-bearing and control hindlimbs were expressed as regional percent injected activity corrected for physical decay (%IA) by reference to concurrently imaged standards, and for 125I-IL-8 by direct tissue counting at necropsy as well. 125I-IL-8 displayed appropriate electrophoretic mobility, retained chemotactic and high-affinity receptor-binding activity in vitro, and exhibited exponentially decreasing activity in most tissues beginning shortly after intravenous injection. Scintigrams showed asymmetrically increased activity in the lesion-bearing hindlimb for all three agents. By scintigraphy, 125I-IL-8 activity in the lesion-bearing hindlimb reached a zenith 1-3 h post-injection at 4.8 +/- 0.5 %IA and decreased exponentially thereafter, with little change in lesioned-to-control limb ratios (mean L/C = 3.0 +/- 0.7) over the imaging period. By direct tissue counting, abscess-associated mean IL-8 activity per gram of tissue increased to four times that of adjacent muscle and nearly seven times that of contralateral muscle by 24 h post-injection. Lesion-bearing hindlimb 111In-WBC activity also rose rapidly, reaching 4.2 +/- 0.6 %IA by scintigraphy at 3 h and an eventual plateau (maximum of 4.5 +/- 0.4 %IA) by 24 h. 67Ga scintigraphic activity in the lesion-bearing hindlimb peaked briefly at 3-6 h post-injection (9.2 +/- 0.5 %IA) and subsequently declined to a constant level of about 7.5 %IA. However, L/C for 111In-WBC and for 67Ga-citrate each averaged only 1.5 +/- 0.3 over the imaging period, compared with a mean L/C of 1.2 +/- 0.2 for a blood pool radiotracer. We conclude that 125I-IL-8 is rapidly and selectively concentrated in regions of acute inflammation, presumably by high-affinity binding to IL-8 receptors on neutrophils within the inflammatory focus. Radioiodinated IL-8 offers an attractive alternative to 67Ga-citrate and 111In-WBC for early imaging of acute inflammatory lesions, and demonstrates significantly higher target-to-nontarget activity ratios in this model. The potential usefulness of radiolabelled IL-8 for clinical scintigraphy should be evaluated.
Hay
R V
RV
Department of Internal Medicine, University of Michigan Veterans' Affairs Medical Center, Ann Arbor, USA.
Skinner
R S
RS
Newman
O C
OC
Kunkel
S L
SL
Lyle
L R
LR
Shapiro
B
B
Gross
M D
MD
D000818:Animals; D002351:Carrageenan; D002951:Citrates; D005260:Female; D005708:Gallium; D005710:Gallium Radioisotopes; D006801:Humans; D007205:Indium Radioisotopes; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging*; D016209:Interleukin-8 / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D017708:Leukocyte Transfusion; D007962:Leukocytes; D008297:Male; D009942:Organometallic Compounds; D015125:Oxyquinoline / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014183:Transplantation, Heterologous
D002951:Citrates; D005710:Gallium Radioisotopes; D007205:Indium Radioisotopes; D016209:Interleukin-8; D007457:Iodine Radioisotopes; D009942:Organometallic Compounds; D011994:Recombinant Proteins; C032950:indium oxine; D015125:Oxyquinoline; D002351:Carrageenan; D005708:Gallium; C103850:gallium citrate