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Theranostics 2014; 4(5):546-555. doi:10.7150/thno.8159 This issue Cite

Research Paper

Longitudinal PET Imaging of Muscular Inflammation Using ¹⁸F-DPA-714 and ¹⁸F-Alfatide II and Differentiation with Tumors

Chenxi Wu^{1, 2}, Xuyi Yue², Lixin Lang², Dale O. Kiesewetter², Fang Li¹, Zhaohui Zhu^1✉, Gang Niu², Xiaoyuan Chen^{2 ✉}

1. Department of Nuclear Medicine, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China.
2. Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, USA

✉ Corresponding author: Zhaohui Zhu, Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing 100730, China. Telephone: 86-10-69154196; E-mail: zhuzhhcn. Xiaoyuan Chen, Laboratory for Molecular Imaging & Nanomedicine, BG 31 RM 1C22 31 Center Dr Bethesda MD 20814. Telephone: 301-451-4246; Email: shawn.chengov More

Abstract

Aim: ¹⁸F-DPA-714 is a PET tracer that recognizes macrophage translocator protein (TSPO), and ¹⁸F-Alfatide II (¹⁸F-AlF-NOTA-E[PEG₄-c(RGDfk)]₂) is specific for integrin α_vβ₃. This study aims to apply these two tracers for longitudinal PET imaging of muscular inflammation, and evaluate the value of ¹⁸F-DPA-714 in differentiating inflammation from tumor.

Methods: RAW264.7 mouse macrophage cells were used for cell uptake analysis of ¹⁸F-DPA-714. A mouse hind limb muscular inflammation model was established by intramuscular injection of turpentine oil. For the inflammation model, PET imaging was performed at different days using ¹⁸F-DPA-714 and ¹⁸F-Alfatide II. The specificity of the imaging probes was tested by co- or pre-injection of PK11195 or unlabeled RGD (Arg-Gly-Asp) peptide. PET imaging using ¹⁸F-DPA-714 was performed in A549, HT29, U87MG, INS-1, and 4T1 xenograft models. Immunofluorescence staining was performed to evaluate infiltrated macrophages and angiogenesis in inflammation and/or tumors.

Results: Uptake of ¹⁸F-DPA-714 in RAW264.7 cells was 45.5% at 1 h after incubation, and could be blocked by PK11195. PET imaging showed increased ¹⁸F-DPA-714 and ¹⁸F-Alfatide II uptake at inflammatory muscles. Peak uptake of ¹⁸F-DPA-714 was seen on day 6 (4.02 ± 0.64 %ID/g), and peak uptake of ¹⁸F-Alfatide II was shown on day 12 (1.87 ± 0.35 %ID/g) at 1 h p.i.. Tracer uptakes could be inhibited by PK11195 for ¹⁸F-DPA-714 or cold RGD for ¹⁸F-Alfatide II. Moreover, macrophage depletion with liposomal clodronate also reduced the local accumulation of both tracers. A549, HT29, U87MG, INS-1, and 4T1 tumor uptakes of ¹⁸F-DPA-714 (0.46 ± 0.28, 0.91 ± 0.08, 1.69 ± 0.67, 1.13 ± 0.33, 1.22 ± 0.55 %ID/g at 1 h p.i., respectively) were significantly lower than inflammation uptake (All P < 0.05).

Conclusion: PET imaging using ¹⁸F-DPA-714 as a TSPO targeting tracer could evaluate the dynamics of macrophage activation and infiltration in different stages of inflammatory diseases. The concomitant longitudinal PET imaging with both ¹⁸F-DPA-714 and ¹⁸F-Alfatide II matched the causal relationship between macrophage infiltration and angiogenesis. Moreover, we found ¹⁸F-DPA-714 uptake in several types of tumors is significantly lower than that in inflammatory muscles, suggesting ¹⁸F-DPA-714 PET has the potential for better differentiation of tumor and non-tumor inflammation.

Keywords: ¹⁸F-DPA-714, ¹⁸F-Alfatide II, positron emission tomography, inflammation, tumor, TSPO

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