Prokineticin Receptor 1 Antagonist PC-10 as a Biomarker for Imaging Inflammatory Pain

Journal of Nuclear Medicine

Cenzo Congiu¹  Dale O. Kiesewetter¹  Valentina Onnis¹  Ido D. Weiss¹  Roberta Lattanzi¹  Severo Salvadori¹  Xiaoyuan Chen¹  Gang Niu¹  Gianfranco Balboni¹  Orit Jacobson¹ 

关键词: prokineticin receptor;    inflammation;    positron emission tomography (PET);    ¹⁸F;   

DOI  :  10.2967/jnumed.110.084772

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Prokineticin receptor 1 (PKR1) and its ligand Bv8 were shown to be expressed in inflammation-induced pain and by tumor-supporting fibroblasts. Blocking this receptor might prove useful for reducing pain and for cancer therapy. However, there is no method to quantify the levels of these receptors in vivo. Methods: A nonpeptidic PKR1 antagonist, N-{2-[5-(4-fluoro-benzyl)-1-(4-methoxy-benzyl)-4,6-dioxo-1,4,5,6-tetrahydro-[1,3,5]triazin-2-ylamino]-ethyl}-guanidine, which contains a free guanidine group, was labeled with 18F by reacting the guanidine function with N-succinimidyl-4-18F-fluorobenzoate to give the guanidinyl amide N-(4-18F-fluoro-benzoyl)-N′-{2-[5-(4-fluoro-benzyl)-1-(4-methoxy-benzyl)-4,6-dioxo-1,4,5,6-tetrahydro-[1,3,5]triazin-2-ylamino]-ethyl}-guanidine (18F-PC-10). Inflammation was induced in C57BL/6 mice by subcutaneous injection of complete Freund adjuvant in the paw. The mice were imaged with 18F-PC-10, 18F-FDG, and 64Cu-pyruvaldehyde bis(4-methyl-3-thiosemicarbazone) (64Cu-PTSM) at 24 h after complete Freund adjuvant injection using a small-animal PET device. Results: 18F-PC-10 was synthesized with a radiochemical yield of 16% ± 3% (decay-corrected). 18F-PC-10 accumulated specifically in the inflamed paw 4- to 5-fold more than in the control paw. Compared with 18F-PC-10, 18F-FDG and 64Cu-PTSM displayed higher accumulation in the inflamed paw but also had higher accumulation in the control paw, demonstrating a reduced signal-to-background ratio. 18F-PC-10 also accumulated in PKR1-expressing organs, such as the salivary gland and gastrointestinal tract. Conclusion: 18F-PC-10 can be used to image PKR1, a biomarker of the inflammation process. However, the high uptake of 18F-PC-10 in the gastrointestinal tract, due to specific uptake and the metabolic processing of this highly lipophilic molecule, would restrict its utility.

【 授权许可】

Unknown