期刊
JOURNAL OF NUCLEAR MEDICINE
卷 60, 期 4, 页码 504-510出版社
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.118.213223
关键词
PET; olaparib; PARP; cancer; molecular imaging
资金
- Pancreatic Cancer U.K.
- Pancreatic Cancer Research Fund
- CRUK through the Oxford Institute for Radiation Oncology
- CRUK Oxford Centre
- CRUK/EPSRC Imaging Centre in Oxford
- EPSRC [EP/L025604/1, NS/A000024/1]
- CRUK [C5255/A16466]
- Royal Society
- Cancer Research U.K.
- EPSRC [EP/L025604/1] Funding Source: UKRI
- MRC [MR/R01695X/1] Funding Source: UKRI
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 F-18-radiofluorination of aryl boronic esters, we accessed, for the first time (to our knowledge), the F-18-radiolabeled isotopolog of the Food and Drug Administration-approved PARP inhibitor olaparib. The use of the F-18-labeled equivalent of olaparib allows direct prediction of the distribution of olaparib, given its exact structural likeness to the native, nonradiolabeled drug. Results: F-18-olaparib was taken up selectively in vitro in PARP-1-expressing cells. Irradiation increased PARP-1 expression and F-18-olaparib uptake in a radiation-dose-dependent fashion. PET imaging in mice showed specific uptake of F-18-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 F-18-olaparib increased by 70% (P = 0.025). Conclusion: Taken together, we show that F-18-olaparib has great potential for noninvasive tumor imaging and monitoring of radiation damage.
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