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Protein Kinase C Imaging Using Carbon-11-Labeled Phorbol Esters: 12-Deoxyphorbol 13-Isobutyrate-20-[1-¹¹C]Butyrate as the Potential Ligand for Positron Emission Tomography

Department of Neurosurgery, Kyoto Prefectural University of Medicine and Nishijin Hospital, Kyoto, Japan
Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan

Correspondence: For reprints or correspondence contact: Yoshio Imahori, MD, PhD, Dept. of Neurosurgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo 602, Kyoto, Japan.

ABSTRACT

Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-¹¹C]butyrate, phorbol 12,13-[1-¹¹C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-¹¹C]butyrate, were synthesized by using [¹¹C]ethylketene with a high specific activity (186GBq/µmol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-(1-¹¹C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of this compound to protein kinase C were confirmed by in vivo displacement studies with unlabeled 12-deoxyphorbol 13-isobutyrate-20-butyrate and unlabeled phorbol 12,13-dibutyrate. This suggests that 12-deoxyphorbol 13-isobutyrate-20-[1-¹¹C] butyrate has a specific binding affinity for protein kinase C.