Current Advances in PARP1-Targeted Theranostics

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.