Effect of the Prosthetic Group on the Pharmacologic Properties of ¹⁸F‑Labeled Rhodamine B, a Potential Myocardial Perfusion Agent for Positron Emission Tomography (PET)

Abstract

We recently reported the development of the 2-[¹⁸F]­fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [¹⁸F]­fluoroethyl prosthetic group, has significant uptake in the myocardium in rats but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared ¹⁸F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of ¹⁸F-labeled compounds. They also support the value of continued investigation of ¹⁸F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging