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J Nucl Med. 2008; 49 (Supplement 1):45P
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Radiopharmaceutical Chemistry: New Chemistry-Other

Novel Radio-metal Chemistry

A bispecific radioligand for inflammation imaging via TNF and IL-1 pathways

Zhonglin Liu1, Matthew Hui2, James Woolfenden1 and Harrison Barrett1

1 University of Arizona, Tucson, Arizona; 2 AmProtein Corporation, Camarillo, California

177

Objectives: Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1) are potent proinflammatory mediators in various diseases including myocardial infarction. Their actions are regulated by soluble TNF receptors (TNFR1/TNFR2) and IL-1 receptor antagonist (IL-1ra). The aim of this study was to characterize the inflammation targeting properties of 99mTc-labeled dual-domain fusion protein, 99mTc-TNFR2-Fc-IL-1ra (TFcI), in comparison with two individual ligands, 99mTc-TNFR2-Fc (TFc) and 99mTc-IL-1ra-Fc (IFc).

Methods: 99mTcO-4 was mixed with stannous glucoheptonate and incubated with thiolated proteins to obtain 99mTc-labeled ligands. Each ligand was studied in 4 rats with carrageenan-induced paw edema. For detection of inflammatory response to ischemia-reperfusion injury, SPECT images with 3 ligands were obtained in 13 rat hearts with acute infarcts.

Results: TFcI exhibited a moderate blood retention compared to TFc and IFc. Higher tracer uptake (%ID/gm) was observed in the paws with edema than that in the controls with saline (TFcI: 0.38±0.10 vs. 0.08±0.01; IFc: 0.11±0.03 vs. 0.05±0.01; TFc: 0.27±0.11 vs. 0.08±0.02, P<0.05). TFcI behaved most aggressively in the inflammatory sites. All 3 ligands showed positive uptake in the hearts with infarcts 2-hr after i.v. injection. A higher uptake pattern of TFcI was observed in the ischemic area as compared to IFc and TFc. The radioactive accumulation (%ID/gm) in the ischemic area and the remote zone was 1.14±0.05 vs. 0.17±0.02 in TFcI; 0.61±0.11 vs. 0.16±0.04 in IFc; and 0.81±0.06 vs. 0.24±0.09 in TFc, P<0.05.

Conclusions: 99mTc-TNFR2-Fc-IL-1ra has a more favorable kinetic profile and potent affinity to inflammatory sites than the individual cytokine ligands. This bispecific ligand may provide a suitable approach for detection of inflammatory response in the ischemia-reperfused hearts.





This Article
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Right arrow Articles by Barrett, H.
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Right arrow Articles by Barrett, H.