PARP and PARPi PET imaging

Cells maintain the integrity of the genome by recognizing DNA damage and repairing DNA. Poly(ADP-ribose) polymerase 1 and 2 (PARP1 and PARP2) are essential enzymes as damage identifiers and signal transducers. When PARP1 binds damaged DNA, its catalytic function is activated, leading to PARylation (addition of negatively charged branched poly(ADP-ribose) chains) and recruitment of DNA repair effectors such as XRCC1, and remodelling of chromatin structure around damaged DNA. Then PARP1 PARylates itself (autoPARylation), causing its detachment from DNA.

PARP1 and PARP2 inhibitors (PARPi) can sensitise tumour cells to radio- and chemotherapy induced DNA damage. Olaparib, rucaparib, niraparib, and talazoparib are PARP inhibitors which interact with the binding site of β-NAD+ in the catalytic domain of PARP1 and PARP2. PARP1 expression can be assessed using PET radioligands such as [18F]fluorthanatrace ([18F]FTT) (Zhou et al., 2014; Edmonds et al., 2016; Michel et al., 2017; Makvandi et al., 2018; McDonald et al., 2020; Young et al., 2022), [18F]PARPi (Carney et al., 2016; Demétrio de Souza França et al., 2020; Young et al., 2020), [18F]FPyPARP (Stotz et al., 2021), and [18F]rucaparib (Chan et al., 2022).

See also:


Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science 2017; 355(6330): 1152-1158. doi: 10.1126/science.aam7344.

Ambur Sankaranarayanan R, Kossatz S, Weber W, Beheshti M, Morgenroth A, Mottaghy FM. Advancements in PARP1 targeted nuclear imaging and theranostic probes. J Clin Med. 2020; 9(7): 2130. doi: 10.3390/jcm9072130.

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Updated at: 2022-12-15
Created at: 2022-01-13
Written by: Vesa Oikonen