# Fluorinated Carnitine Derivatives as Tools to Visualise Carnitine Transport and Metabolism

## TL;DR

Scientists created fluorinated carnitine compounds to track how cells use carnitine, which is important for energy production and linked to diseases like cancer.

## Contribution

The paper introduces fluoromethylcarnitine (FMC) and its radiolabeled form [18F]FMC as novel tools for studying carnitine transport and metabolism.

## Key findings

- FMC and [18F]FMC can measure carnitine transport and metabolism in cells and living subjects.
- [18F]FMC PET imaging reveals increased carnitine use in a lung cancer model.
- Fluorine labeling enables multimodal detection of carnitine biology.

## Abstract

Carnitine and its acyl derivatives are essential for the transport of fatty acids from the cytosol into the mitochondrial matrix for β‐oxidation, which supplies the cell with energy. Altered transport and metabolism of carnitine are associated with multiple diseases and disorders, including heart disease, insulin resistance, and cancer. Fluorinated carnitine derivatives have the potential to measure aberrant carnitine metabolism in these disorders using 19F‐NMR and mass spectrometry. Furthermore, by radiolabeling carnitines with fluorine‐18, altered carnitine utilisation may be visualised in vivo using positron emission tomography (PET) imaging. Here, the design and synthesis of a fluorinated carnitine derivative, fluoromethylcarnitine (FMC), and its radiolabelled equivalent, [18F]fluoromethylcarnitine ([18F]FMC), are described, and their ability to quantitatively measure carnitine transport and downstream metabolism in a variety of settings are shown, from simple cell models to living subjects. Finally, [18F]FMC PET is used to visualise elevated carnitine utilisation in a xenograft model of non‐small cell lung cancer.

Fluorinated carnitines, fluoromethyl carnitine (FMC) and [18F]fluoromethyl carnitine ([18F]FMC), are synthesised and established as powerful probes to interrogate carnitine biology. The multimodal detection facilitated by fluorine labelling, including 19F NMR, mass spectrometry, and positron emission tomography imaging, allowed for visualisation of carnitine utilisation in a range of systems, from simple cells to living subjects.