# Synthesis and 64Cu‐Radiolabeling Strategies of Small Organic Radioconjugates Based on the AMD070 Scaffold

## TL;DR

Researchers developed two new radiopharmaceuticals using the AMD070 scaffold and a copper chelator for potential use in PET imaging of cancer cells.

## Contribution

The paper introduces two novel 64Cu-radioconjugates for CXCR4-targeted PET imaging using the AMD070 scaffold.

## Key findings

- Two new CXCR4-targeted 64Cu-radioconjugates were synthesized using the AMD070 scaffold and te1pa chelator.
- The radiolabeling process was optimized for potential in vitro and in vivo studies.
- This approach expands the range of small organic inhibitors for PET imaging applications.

## Abstract

CXCR4 is a transmembrane receptor overexpressed in a large variety of cancer cells. In addition to classical antibody‐ and peptide‐targeting for the development of positron emission tomography (PET) radiopharmaceuticals, this receptor possesses a range of small organic inhibitors that can be exploited. These are based mainly on nitrogen‐rich scaffolds, such as AMD070, and cyclic polyamines, such as cyclam, in the AMD3100 skeleton. The latter has been explored as a direct 64Cu chelator, but examples of CXCR4 PET imaging with small organic targeting units are still scarce in the literature. Herein, the synthesis of two novel CXCR4‐directed radiopharmaceuticals is described, combining the AMD070 scaffold as a targeting unit and bifunctional te1pa macrocycle as a strong 64Cu chelator. The synthesis of the conjugates and optimization of 64Cu‐radiolabeling are presented, opening the way for future in vitro and in vivo studies.

Two novel 64Cu‐radioconjugates have been prepared, based on the AMD070 scaffold as a targeting unit and cyclam‐based te1pa chelator, for future applications in positron emission tomography imaging. Synthesis of ligands and their 64Cu‐radiolabeling are described herein.© 2025 WILEY‐VCH GmbH