PT  - JOURNAL ARTICLE
AU  - Huub J.J.M. Rennen
AU  - Otto C. Boerman
AU  - Wim J.G. Oyen
AU  - Jos W.M. van der Meer
AU  - Frans H.M. Corstens
TI  - Specific and Rapid Scintigraphic Detection of Infection with <sup>99m</sup>Tc-Labeled Interleukin-8
DP  - 2001 Jan 01
TA  - Journal of Nuclear Medicine
PG  - 117--123
VI  - 42
IP  - 1
4099  - http://jnm.snmjournals.org/content/42/1/117.short
4100  - http://jnm.snmjournals.org/content/42/1/117.full
SO  - J Nucl Med2001 Jan 01; 42
AB  - 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.