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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2022

Open Access 26-05-2022 | Pancreatic Cancer | Original Article

Imaging PARP with [18F]rucaparib in pancreatic cancer models

Authors: Chung Ying Chan, Zijun Chen, Gianluca Destro, Mathew Veal, Doreen Lau, Edward O’Neill, Gemma Dias, Michael Mosley, Veerle Kersemans, Florian Guibbal, Véronique Gouverneur, Bart Cornelissen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2022

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Abstract

Purpose

Rucaparib, an FDA-approved PARP inhibitor, is used as a single agent in maintenance therapy to provide promising treatment efficacy with an acceptable safety profile in various types of BRCA-mutated cancers. However, not all patients receive the same benefit from rucaparib-maintenance therapy. A predictive biomarker to help with patient selection for rucaparib treatment and predict clinical benefit is therefore warranted. With this aim, we developed [18F]rucaparib, an 18F-labelled isotopologue of rucaparib, and employed it as a PARP-targeting agent for cancer imaging with PET. Here, we report the in vitro and in vivo evaluation of [18F]rucaparib in human pancreatic cancer models.

Method

We incorporated the positron-emitting 18F isotope into rucaparib, enabling its use as a PET imaging agent. [18F]rucaparib binds to the DNA damage repair enzyme, PARP, allowing direct visualisation and measurement of PARP in cancerous models before and after PARP inhibition or other genotoxic cancer therapies, providing critical information for cancer diagnosis and therapy. Proof-of-concept evaluations were determined in pancreatic cancer models.

Results

Uptake of [18F]rucaparib was found to be mainly dependent on PARP1 expression. Induction of DNA damage increased PARP expression, thereby increasing uptake of [18F]rucaparib. In vivo studies revealed relatively fast blood clearance of [18F]rucaparib in PSN1 tumour-bearing mice, with a tumour uptake of 5.5 ± 0.5%ID/g (1 h after i.v. administration). In vitro and in vivo studies showed significant reduction of [18F]rucaparib uptake by addition of different PARP inhibitors, indicating PARP-selective binding.

Conclusion

Taken together, we demonstrate the potential of [18F]rucaparib as a non-invasive PARP-targeting imaging agent for pancreatic cancers.
Appendix
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Metadata
Title
Imaging PARP with [18F]rucaparib in pancreatic cancer models
Authors
Chung Ying Chan
Zijun Chen
Gianluca Destro
Mathew Veal
Doreen Lau
Edward O’Neill
Gemma Dias
Michael Mosley
Veerle Kersemans
Florian Guibbal
Véronique Gouverneur
Bart Cornelissen
Publication date
26-05-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05835-4

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