Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging

Abstract Background Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as a promising class of therapeutics, particularly in the treatment of cancers with defective DNA repair mechanisms, such as those with breast cancer genes (BRCA) mutations. Their effectiveness in cancer therapy is now w...

Full description

Saved in:
Bibliographic Details
Main Authors: Gianluca Destro, Rebecca Rizzo, Chiara Rua, Raha Rouhbakhsh Azimi, Silvia Morbelli
Format: Article
Language:English
Published: SpringerOpen 2025-07-01
Series:EJNMMI Radiopharmacy and Chemistry
Subjects:
Online Access:https://doi.org/10.1186/s41181-025-00364-5
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849767229859561472
author Gianluca Destro
Rebecca Rizzo
Chiara Rua
Raha Rouhbakhsh Azimi
Silvia Morbelli
author_facet Gianluca Destro
Rebecca Rizzo
Chiara Rua
Raha Rouhbakhsh Azimi
Silvia Morbelli
author_sort Gianluca Destro
collection DOAJ
description Abstract Background Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as a promising class of therapeutics, particularly in the treatment of cancers with defective DNA repair mechanisms, such as those with breast cancer genes (BRCA) mutations. Their effectiveness in cancer therapy is now well-established, but the ongoing advancements in radiochemistry are expanding their potential to combine both therapeutic and imaging capabilities. Radiolabelled PARP inhibitors, used in conjunction with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), might enable precise imaging of PARP expression in tumours, potentially providing invaluable insights into treatment response, tumor heterogeneity, and molecular profiling. Main body The radiochemistry of PARP inhibitors involves incorporating radioisotopes (most of all Fluorine-18) into the molecular structure of these molecules. The first strategy used to achieve this goal was the use of prosthetic groups bearing the fluorine-18. Then, the development of radioisotopologue have gained ground, followed later by the replacement with other halogens such as bromine, iodine, or astatine has taken place. Another frontier is represented by the metal radiolabelling of these inhibitors through the introduction of a chelator moiety to these molecules, thus further expanding both imaging and therapy applications. Conclusion Finally, emerging evidence suggest the possibility to involve PARP-related radiopharmaceuticals in theranostics approaches. Despite challenges such as the complexity of radiolabelling, regulatory hurdles, and the need for more robust clinical validation, the continued exploration of the radiochemistry of PARP inhibitors promises to revolutionize both the diagnosis and treatment of cancer, offering hope for more effective and personalized cancer care.
format Article
id doaj-art-8f38b37b62ce4f978d47feb06803c7f2
institution DOAJ
issn 2365-421X
language English
publishDate 2025-07-01
publisher SpringerOpen
record_format Article
series EJNMMI Radiopharmacy and Chemistry
spelling doaj-art-8f38b37b62ce4f978d47feb06803c7f22025-08-20T03:04:17ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2025-07-0110113310.1186/s41181-025-00364-5Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imagingGianluca Destro0Rebecca Rizzo1Chiara Rua2Raha Rouhbakhsh Azimi3Silvia Morbelli4Department of Molecular Biotechnology and Health Sciences, University of TurinDepartment of Molecular Biotechnology and Health Sciences, University of TurinDepartment of Molecular Biotechnology and Health Sciences, University of TurinDepartment of Molecular Biotechnology and Health Sciences, University of TurinDepartment of Nuclear Medicine, University of TurinAbstract Background Poly (ADP-ribose) polymerase (PARP) inhibitors have emerged as a promising class of therapeutics, particularly in the treatment of cancers with defective DNA repair mechanisms, such as those with breast cancer genes (BRCA) mutations. Their effectiveness in cancer therapy is now well-established, but the ongoing advancements in radiochemistry are expanding their potential to combine both therapeutic and imaging capabilities. Radiolabelled PARP inhibitors, used in conjunction with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), might enable precise imaging of PARP expression in tumours, potentially providing invaluable insights into treatment response, tumor heterogeneity, and molecular profiling. Main body The radiochemistry of PARP inhibitors involves incorporating radioisotopes (most of all Fluorine-18) into the molecular structure of these molecules. The first strategy used to achieve this goal was the use of prosthetic groups bearing the fluorine-18. Then, the development of radioisotopologue have gained ground, followed later by the replacement with other halogens such as bromine, iodine, or astatine has taken place. Another frontier is represented by the metal radiolabelling of these inhibitors through the introduction of a chelator moiety to these molecules, thus further expanding both imaging and therapy applications. Conclusion Finally, emerging evidence suggest the possibility to involve PARP-related radiopharmaceuticals in theranostics approaches. Despite challenges such as the complexity of radiolabelling, regulatory hurdles, and the need for more robust clinical validation, the continued exploration of the radiochemistry of PARP inhibitors promises to revolutionize both the diagnosis and treatment of cancer, offering hope for more effective and personalized cancer care.https://doi.org/10.1186/s41181-025-00364-5PARPPARP1PARP inhibitorRadiolabellingPARP imagingPARP therapy
spellingShingle Gianluca Destro
Rebecca Rizzo
Chiara Rua
Raha Rouhbakhsh Azimi
Silvia Morbelli
Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging
EJNMMI Radiopharmacy and Chemistry
PARP
PARP1
PARP inhibitor
Radiolabelling
PARP imaging
PARP therapy
title Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging
title_full Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging
title_fullStr Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging
title_full_unstemmed Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging
title_short Exploring the radiochemistry of PARP inhibitors: a new era in therapy and imaging
title_sort exploring the radiochemistry of parp inhibitors a new era in therapy and imaging
topic PARP
PARP1
PARP inhibitor
Radiolabelling
PARP imaging
PARP therapy
url https://doi.org/10.1186/s41181-025-00364-5
work_keys_str_mv AT gianlucadestro exploringtheradiochemistryofparpinhibitorsaneweraintherapyandimaging
AT rebeccarizzo exploringtheradiochemistryofparpinhibitorsaneweraintherapyandimaging
AT chiararua exploringtheradiochemistryofparpinhibitorsaneweraintherapyandimaging
AT raharouhbakhshazimi exploringtheradiochemistryofparpinhibitorsaneweraintherapyandimaging
AT silviamorbelli exploringtheradiochemistryofparpinhibitorsaneweraintherapyandimaging