Dataset Information

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

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.

SUBMITTER: Chan CY

PROVIDER: S-EPMC9399069 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Imaging PARP with [<sup>18</sup>F]rucaparib in pancreatic cancer models.

Chan Chung Ying CY Chen Zijun Z Destro Gianluca G Veal Mathew M Lau Doreen D O'Neill Edward E Dias Gemma G Mosley Michael M Kersemans Veerle V Guibbal Florian F Gouverneur Véronique V Cornelissen Bart B

European journal of nuclear medicine and molecular imaging 20220526 11

<h4>Purpose</h4>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 [<sup>18</sup>F]rucaparib, an ...[more]

PMID: 35614267

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Dataset Information

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

Purpose

Method

Results

Conclusion

Publications

Imaging PARP with [<sup>18</sup>F]rucaparib in pancreatic cancer models.

Similar Datasets

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Dataset Information

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

Purpose

Method

Results

Conclusion

Publications

Imaging PARP with [<sup>18</sup>F]rucaparib in pancreatic cancer models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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