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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

Synthesis and Preliminary Evaluations of [18F]fluorinated Pyridine-2- carboxamide Derivatives for Targeting PD-L1 in Cancer

Author(s): Philipp Maier, Gabriele Riehl, Ina Israel and Samuel Samnick*

Volume 23, Issue 5, 2023

Published on: 14 November, 2022

Page: [412 - 424] Pages: 13

DOI: 10.2174/1568009623666221021121014

Price: $65

Abstract

Background: Treatment with immune checkpoint inhibitors has improved both progressionfree survival and overall survival in a subset of patients with tumors. However, the selection of patients who benefit from immune checkpoint inhibitor treatment remains challenging. Positron Emission Tomography (PET) is a non-invasive molecular imaging tool that offers a promising alternative to the current IHC for detecting the PD-L1 expression in malignant cells in vivo, enabling patient selection and predicting the response to individual patient immunotherapy treatment.

Objectives: Herein, we report the development of novel [18F]labeled pyridine-2-carboxamide derivatives [18F]2 and [18F]3 as small-molecule probes for imaging immune checkpoint (PD-1/PD-L1) in cancer using PET.

Methods and Results: [18F]2 and [18F]3 were prepared by a one-step radiofluorination in 44 ± 5% and 30 ± 4% radiochemical yield and > 98% radiochemical purity for a potential clinical translation. The total synthesis time, including HPLC purification, was less than 45 min. [18F]2 and [18F]3 showed excellent stability in injection solution and a significant accumulation and retention in PD-1/PD-L1 expressing MDA-MB-231 breast cancer and in HeLa cervix carcinoma cells (2- 5 cpm/1000 cells). In addition, autoradiographic analysis and inhibition experiments on tumor slices confirm the potential of both compounds as specific imaging probes for the PD-1/PD-L1 axis in tumors.

Conclusion: The in vitro evaluation in PD-L1 expressing cells together with results from autoradiographic analysis in PD-L1 positive tumor sections, suggest that [18F]2 and [18F]3 could be potential imaging probes for assessing PD-L1 expression in tumors and warrant further biological evaluations in vivo.

Keywords: Immune checkpoint imaging, PD-1/PD-L1, positron emission tomography, autoradiography, MDA-MB-231, HeLa, LNCap cell lines.

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