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Current Advances in PARP1-Targeted Theranostics.

Jie Tong¹, Baosheng Chen¹, Tommaso Volpi¹

¹Yale PET Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, Connecticut, USA.

Journal of Labelled Compounds & Radiopharmaceuticals

|February 25, 2025

Summary

This summary is machine-generated.

Poly (ADP-ribose) polymerase 1 (PARP1) is crucial for DNA repair and targeted by cancer therapies. New PARP1 imaging agents that cross the blood-brain barrier are needed for brain cancer diagnosis and treatment.

Keywords:

PARP1 blood brain barrier (BBB)positron emission tomography (PET)theranostics

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Area of Science:

Biochemistry and Molecular Biology
Oncology
Radiopharmaceutical Science

Background:

Poly (ADP-ribose) polymerase 1 (PARP1) is vital for DNA repair, chromatin regulation, and cellular homeostasis.
PARP1 activity, through PARylation, impacts cellular responses to oxidative stress and DNA damage, influencing survival and inflammation.
PARP inhibitors (PARPis) show efficacy in cancers with homologous recombination repair defects, such as BRCA-mutated cancers.

Purpose of the Study:

To review radiopharmaceuticals and radioligands targeting PARP1 for diagnostic and therapeutic applications.
To highlight the need for blood-brain barrier (BBB)-penetrant PARP1 tracers for neurooncology.
To discuss the potential of BBB-penetrant PARP1 tracers in diagnosing and treating brain cancers and other neurological disorders.

Main Methods:

Literature review of PARP1-targeted radiopharmaceuticals and radioligands.
Analysis of pharmacological characteristics and clinical utility of existing PARP1 tracers.
Evaluation of PARP1 tracers capable of crossing the BBB.

Main Results:

PARP1 is a validated therapeutic target in oncology and CNS disorders.
PARP1-targeted PET imaging aids in patient stratification and treatment monitoring.
Development of BBB-penetrant PARP1 tracers is crucial for advancing neuro-oncology.

Conclusions:

PARP1-targeted theranostics represent a significant step in personalized oncology.
Limited BBB penetration restricts current PARP1 imaging applications in brain tumors.
BBB-penetrant PARP1 tracers hold promise for neuroimaging and neurological disorder management.