Labeling Method Largely Affects the Imaging Potential of Interleukin-8

TO THE EDITOR:

We read with interest the study by Gross et al. entitled “Imaging of Human Infection with ¹³¹I-Labeled Recombinant Human Interleukin-8” (1). The authors conducted a pilot study with ¹³¹I-labeled IL-8 for detection of infection in patients. The data nicely showed that this IL-8 preparation could visualize infectious foci in patients with osteomyelitis and cellulitis. Furthermore, the agent appeared to be safe, since no significant side effects were observed on intravenous administration. Apparently, the study was performed years before the present publication (2). In the meantime we studied several aspects related to labeling IL-8 for detection of infection.

We have shown that the labeling method used in this study is rather suboptimal for IL-8 and that substantial improvements can be obtained using alternative labeling strategies. IL-8 was radioiodinated according to the chloramine-T method (3). This method results in iodination of the tyrosine residues similar to the IODO-GEN method. We pointed out that the radioiodination method clearly affected the in vivo biodistribution of IL-8 (4). IL-8 radioiodinated by the Bolton-Hunter method showed superior characteristics for infection imaging compared with IL-8 radioiodinated by the IODO-GEN method. In a rabbit model of E. coli-induced soft-tissue infection, abscess-to-background ratios as determined by region-of-interest analysis of the images were 3 for ¹²³I-IL-8 (IODO-GEN method) versus 13 for ¹²³I-IL-8 (Bolton-Hunter method) at 8 h after injection. As pointed out by the authors themselves, labeling IL-8 with ¹²³I would have been a better choice instead of labeling with ¹³¹I. The physical properties of ¹³¹I limit spatial resolution.

The authors made the suggestion that IL-8 labeled with a radiometal instead of iodine may be preferable as an infection imaging agent. Indeed, preclinical studies in our laboratory with ^99mTc-labeled IL-8 showed excellent imaging characteristics for this preparation, with abscess-to-background ratios of up to 22 at 8 h after injection (5). Studies in patients using ^99mTc-labeled IL-8 are planned to evaluate the efficacy of this particular preparation in visualizing inflammatory foci in humans.