Specific and Rapid Scintigraphic Detection of Infection with 99mTc-Labeled Interleukin-8

Journal of Nuclear Medicine

Frans H.M. Corstens¹  Wim J.G. Oyen¹  Jos W.M. van der Meer¹  Huub J.J.M. Rennen¹  Otto C. Boerman¹ 

[1] Departments of Nuclear Medicine and Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands Departments of Nuclear Medicine and Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands Departments of Nuclear Medicine and Internal Medicine, University Medical Center Nijmegen, Nijmegen, The Netherlands

关键词: interleukin-8;    infection;    scintigraphic imaging;    biodistribution;    ^99mTc;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Interleukin-8 (IL-8) is a chemotactic cytokine involved in activation and recruitment of neutrophils to areas of infection. In our previous studies in rabbits we tested 123I-labeled IL-8 for its potential to image infections and showed that IL-8 rapidly and efficiently accumulated in infectious foci. However, labeling of IL-8 with 123I is costly and laborious and the specific activity of the preparation was low. In this study IL-8 was labeled with 99mTc through the hydrazinonicotinamide (HYNIC) chelator. Methods: The leukocyte receptor-binding capacity of the preparation was determined in vitro. Rabbits with Escherichia coli abscesses were injected intravenously with 7 MBq 99mTc-HYNIC-IL-8. Biodistribution of the radiolabel was determined by gamma camera imaging and tissue counting at 8 h after injection. 99mTc-HYNIC-lysozyme was used as a size-matched control. Results: The leukocyte receptor-binding capacity of the 99mTc-HYNIC-IL-8 preparation was preserved as determined in vitro, but labeling efficiency was modest with a specific activity of 3 MBq/μg. 99mTc-HYNIC-IL-8 accumulated rapidly in the abscess up to 0.33 ± 0.06 percentage injected dose per gram (%ID/g) at 8 h after injection (vs. 0.025 ± 0.003 %ID/g for 99mTc-HYNIC-lysozyme). Total uptake in the abscess was 4.9 ± 0.7 %ID (vs. 0.44 ± 0.05 %ID for 99mTc-HYNIC-lysozyme). Abscess-to-contralateral muscle ratios increased up to 127 ± 23 (compared with 6.7 ± 1.1 for 99mTc-HYNIC-lysozyme) and abscess-to-blood ratios increased to 11.9 ± 2.2 (0.24 ± 0.03 for 99mTc-HYNIC-lysozyme). The radiolabel was excreted renally, with a retention in the kidneys of 28 %ID. Gamma camera imaging rapidly visualized the abscess from 1 h after injection onward, with abscess-to-background ratios improving with time up to 22 at 8 h after injection (vs. 2.7 for 99mTc-HYNIC-lysozyme), as determined by quantitative analysis of the images. Most important, only a transient (30 min) moderate drop of leukocyte counts and no leukocytosis were observed after injection of an imaging dose of 99mTc-HYNIC-IL-8. Conclusion: IL-8 can be labeled with 99mTc using HYNIC as a chelator. By this method the leukocyte receptor-binding capacity is preserved. The preparation allows rapid visualization of infection in a rabbit model with high target-to-background ratios. The mild transient drop of leukocyte counts and the absence of leukocytosis suggest that 99mTc-HYNIC-IL-8 may be used as an imaging agent with only mild and transient side effects.

【 授权许可】

Unknown