Iodinated Choline Transport-Targeted Tracers

Abstract

We present a novel series of radioiodinated tracers and potential theranostics for diseases accompanied by pathological function of proteins involved in choline transport. Unlike choline analogues labeled with 11C or 18F that are currently used in the clinic, the iodinated compounds described herein are applicable in positron emission tomography, single-photon emission computed tomography, and potentially in therapy, depending on the iodine isotope selection. Moreover, favorable half-lives of iodine isotopes result in much less challenging synthesis by isotope exchange reaction. Six of the described compounds were nanomolar ligands, and the best compound possessed an affinity 100-fold greater than that of choline. Biodistribution data of 125I-labeled ligands in human prostate carcinoma bearing (PC-3) mice revealed two compounds with a biodistribution profile superior to that of [18F]­fluorocholine.

Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH)

“…PET variables including TBR-wsum predicted the duration of survival, depending on individual lesion response. Future studies should elaborate how this variable, together with progression (escape of the resistant lesion(s)) on PET influences progression-free and overall survival in a larger patient cohort and encourages exploration of choline-transport-targeted theranostics as recently suggested [43].…”