SCINTIGRAPHY OF ACUTE INFLAMMATORY LESIONS IN RATS WITH RADIOLABELED RECOMBINANT HUMAN INTERLEUKIN-8

We compared I-125-labelled recombinant human interleukin-8 (I-125-IL-8 ) with In-111-labelled human leukocytes (In-111-WBC) and Ga-67-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 In-111-oxine. Inflammatory lesions were induced in male rats by subcutaneous injection of 2% carrageenan suspension into their left hindlimbs. Twenty-four hours later, each r at received 1.8-3.7 MBq (50-100 mu Ci) of a single agent by intravenou s 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 correc ted for physical decay (%IA) by reference to concurrently imaged stand ards, and for I-125-IL-8 by direct tissue counting at necropsy as well . (IL)-I-125-8 displayed appropriate electrophoretic mobility, retaine d chemotactic and high-affinity receptor-binding activity in vitro, an d exhibited exponentially decreasing activity in most tissues beginnin g shortly after intravenous injection. Scintigrams showed asymmetrical ly increased activity in the lesion-bearing hindlimb for all three age nts. By scintigraphy, I-125-IL-8 activity in the lesion-bearing hindli mb reached a zenith 1-3 h post-injection at 4.8 +/- 0.5 %IA and decrea sed exponentially thereafter, with little change in lesioned-to-contro l limb ratios (mean L/C = 3.0 +/- 0.7) over the imaging period. By dir ect tissue counting, abscess-associated mean IL-8 activity per gram of tissue increased to four times that of adjacent muscle and nearly sev en times that of contralateral muscle by 24 h post-injection. Lesion-b earing hindlimb In-111-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. Ga-67 scintigraphic activity in the lesion-be aring 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. Howe ver, L/C for In-111-WBC and for Ga-67-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 I-125-IL-8 is rapidly and selectively concentrated in regions of acute inflammation, presum ably by high-affinity binding to IL-8 receptors on neutrophils within the inflammatory focus. Radioiodinated IL-8 offers an attractive alter native to Ga-67-citrate and In-111-WBC for early imaging of acute infl ammatory lesions, and demonstrates significantly higher target-to-nont arget activity ratios in this model. The potential usefulness of radio labelled IL-8 for clinical scintigraphy should be evaluated.