Synthesis and characterization of F-18 labeled indicators for non-invasive in vivo pH measurement

Objectives Preparation of F-18 labeled pH indicators, novel probes for in vivo pH measurement in biological objects.

Methods We performed a reaction of direct fluorination of phenolsulfonphthalein and cresolsulfonphthaleins by [F-18]F2 in acetic acid. The reaction products were separated and characterized by HPLC, mass-spectroscopy, NMR, and UV-VIS spectroscopy

Results Using this method, we synthesized 9 new F-18 labeled compounds, which are mono-, di-, and tri-fluorinated phenolsulfonphthalein, and o- and m-cresolsulfonphthaleins. The compounds have specific activity 1.5-5 Ci/mmol and act like pH indicators with pKa values in a biologically important range of 6-8 and absorption maxima of basic forms at 570-595 nm.

Conclusions We developed a new fluorination reaction and used it to synthesize positron-emitting pH indicators. This new class of pH probes is useful for non-invasive in vivo pH measurement in biological objects based on combination of optical and PET imaging. Positron-emitting pH indicators also allow to perform a one-step pH measurement using differential quenching of Cerenkov luminescence , emitted in biological tissues by positrons, produced during a decay of 18F label