Dataset Information

PET Imaging of PARP Expression Using ¹⁸F-Olaparib.

ABSTRACT: Poly(ADP-ribose) polymerase (PARP) inhibitors are increasingly being studied as cancer drugs, as single agents, or as a part of combination therapies. Imaging of PARP using a radiolabeled inhibitor has been proposed for patient selection, outcome prediction, dose optimization, genotoxic therapy evaluation, and target engagement imaging of novel PARP-targeting agents. Methods: Here, via the copper-mediated ¹⁸F-radiofluorination of aryl boronic esters, we accessed, for the first time (to our knowledge), the ¹⁸F-radiolabeled isotopolog of the Food and Drug Administration-approved PARP inhibitor olaparib. The use of the ¹⁸F-labeled equivalent of olaparib allows direct prediction of the distribution of olaparib, given its exact structural likeness to the native, nonradiolabeled drug. Results: ¹⁸F-olaparib was taken up selectively in vitro in PARP-1-expressing cells. Irradiation increased PARP-1 expression and ¹⁸F-olaparib uptake in a radiation-dose-dependent fashion. PET imaging in mice showed specific uptake of ¹⁸F-olaparib in tumors expressing PARP-1 (3.2% ± 0.36% of the injected dose per gram of tissue in PSN-1 xenografts), correlating linearly with PARP-1 expression. Two hours after irradiation of the tumor (10 Gy), uptake of ¹⁸F-olaparib increased by 70% (P = 0.025). Conclusion: Taken together, we show that ¹⁸F-olaparib has great potential for noninvasive tumor imaging and monitoring of radiation damage.

SUBMITTER: Wilson TC

PROVIDER: S-EPMC6448459 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

PET Imaging of PARP Expression Using 18F-Olaparib.

Wilson Thomas C TC Xavier Mary-Ann MA Knight James J Verhoog Stefan S Torres Julia Baguña JB Mosley Michael M Hopkins Samantha L SL Wallington Sheena S Allen Phillip D PD Kersemans Veerle V Hueting Rebekka R Smart Sean S Gouverneur Véronique V Cornelissen Bart B

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20181102 4

Poly(ADP-ribose) polymerase (PARP) inhibitors are increasingly being studied as cancer drugs, as single agents, or as a part of combination therapies. Imaging of PARP using a radiolabeled inhibitor has been proposed for patient selection, outcome prediction, dose optimization, genotoxic therapy evaluation, and target engagement imaging of novel PARP-targeting agents. Methods: Here, via the copper-mediated 18F-radiofluorination of aryl boronic esters, we accessed, for the first ...[more]

PMID: 30389822

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Project description:BackgroundCardiac PET has recently found novel applications in coronary atherosclerosis imaging using [18F]NaF as a radiotracer, highlighting vulnerable plaques. However, the resulting uptakes are relatively small, and cardiac motion and respiration-induced movement of the heart can impair the reconstructed images due to motion blurring and attenuation correction mismatches. This study aimed to apply an MR-based motion compensation framework to [18F]NaF data yielding high-resolution motion-compensated PET and MR images.MethodsFree-breathing 3-dimensional Dixon MR data were acquired, retrospectively binned into multiple respiratory and cardiac motion states, and split into fat and water fraction using a model-based reconstruction framework. From the dynamic MR reconstructions, both a non-rigid cardiorespiratory motion model and a motion-resolved attenuation map were generated and applied to the PET data to improve image quality. The approach was tested in 10 patients and focal tracer hotspots were evaluated concerning their target-to-background ratio, contrast-to-background ratio, and their diameter.ResultsMR-based motion models were successfully applied to compensate for physiological motion in both PET and MR. Target-to-background ratios of identified plaques improved by 7 ± 7%, contrast-to-background ratios by 26 ± 38%, and the plaque diameter decreased by -22 ± 18%. MR-based dynamic attenuation correction strongly reduced attenuation correction artefacts and was not affected by stent-related signal voids in the underlying MR reconstructions.ConclusionsThe MR-based motion correction framework presented here can improve the target-to-background, contrast-to-background, and width of focal tracer hotspots in the coronary system. The dynamic attenuation correction could effectively mitigate the risk of attenuation correction artefacts in the coronaries at the lung-soft tissue boundary. In combination, this could enable a more reproducible and reliable plaque localisation.

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PET Imaging of PARP Expression Using ¹⁸F-Olaparib.

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OmicsDI is part of the ELIXIR infrastructure

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