Prokineticin receptors antagonist PC-10 as a biomarker for imaging inflammatory pain

Objectives Prokineticin receptors (PKR1/2) and their ligand Bv8 were shown to be expressed in pain related inflammation, as well as by tumor supporting fibroblast. Blocking the receptors might prove useful for reducing pain as well as anti-cancerous therapy. However, there is no method to quantify the levels of these receptors in vivo in order to decide on appropriate treatment candidates.

Methods The non-peptidic PKR1 antagonist (J. Med. Chem 2008, 51 7635-7639), PC-10 was labeled with F-18 by coupling a precursor containing free guanidine group to N-succinimidyl-4-18F-fluorobenzoate (18F-SFB), to give 18F-PC-10. Inflammation related pain was induced in C57Bl/6 mice by intradermal injection of complete freund’s adjuvant (CFA) in the ear, which results in up-regulation of PKR1 in 24 h. In addition, CFA injection induces inflammation in the salivary glands at later time points. Mice were imaged with 18F-PC-10 using a small animal PET six days post CFA injection.

Results 18F-PC-10 was synthesized with radiochemical yield of 9±3% based on 18F-SFB coupling. 18F-PC-10 accumulated in the salivary glands of CFA injected but in those of control mice. 18F-PC-10 was also visualized in metabolic organs.

Conclusions 18F-PC-10 is a promising agent for imaging inflammation process, and should be further characterized for its potential use as an imaging agent of pain and of tumors and tumor supporting fibroblasts