Preclinical evaluation of the potential PARP-imaging probe [carbonyl-11C]DPQ
- Katarína Benčurová 1,2, Theresa Balber 3,4, Victoria Weissenböck 1, Lukas Kogler 1,5, Joachim Friske 6, Verena Pichler 7, Markus Mitterhauser 1,2,8, Marcus Hacker 1, Cécile Philippe 1,2, Marius Ozenil 1
- Katarína Benčurová 1,2, Theresa Balber 3,4, Victoria Weissenböck 1
- 1Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
- 2Joint Applied Medicinal Radiochemistry Facility, University of Vienna, Medical University of Vienna, Vienna, Austria.
- 3Joint Applied Medicinal Radiochemistry Facility, University of Vienna, Medical University of Vienna, Vienna, Austria. theresa.balber@meduniwien.ac.at.
- 4Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Level 3L, Waehringer Guertel 18-20, 1090, Vienna, Austria. theresa.balber@meduniwien.ac.at.
- 5CBmed GmbH-Center for Biomarker Research in Medicine, Graz, Austria.
- 6Division of Molecular and Structural Preclinical Imaging, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
- 7Division of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.
- 8Department for Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.
- 0Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
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View abstract on PubMed
Summary
This summary is machine-generated.[carbonyl-<sup>11</sup>C]DPQ was investigated as a novel positron emission tomography (PET) tracer for poly (ADP-ribose) polymerase-1 (PARP-1) expression. The tracer showed poor tumor accumulation and significant liver metabolism in preclinical models, indicating it is not suitable for further development.
Area Of Science
- Nuclear medicine
- Radiochemistry
- Oncology
Background
- Poly (ADP-ribose) polymerase (PARP) enzymes are critical for DNA repair and are therapeutic targets in cancers like prostate cancer.
- Positron emission tomography (PET) tracers are used for non-invasive monitoring of PARP-1 expression.
- [carbonyl-<sup>11</sup>C]DPQ was developed as a novel PET tracer with a distinct chemical structure compared to existing agents.
Purpose Of The Study
- To preclinically evaluate [carbonyl-<sup>11</sup>C]DPQ as a PET tracer for PARP-1 expression.
- To assess its potential as an alternative to [<sup>18</sup>F]FluorThanatrace and [<sup>18</sup>F]PARPi.
Main Methods
- Synthesis of [carbonyl-<sup>11</sup>C]DPQ using a GE TracerLab FXC2 module.
- Assessment of radiochemical yield, molar activity, and purity.
- In vitro stability testing (formulation, plasma, liver microsomes).
- In vitro cell uptake studies (PC3 prostate cancer cells, CHO-K1 cells).
- In vivo evaluation using a fertilized chicken egg (in ovo) model with PC3 xenografts.
Main Results
- [carbonyl-<sup>11</sup>C]DPQ was successfully synthesized with high yield, molar activity, and purity (>97%).
- The tracer demonstrated good stability in formulation, plasma, and liver microsomes.
- In vitro studies showed similar uptake in cancer and non-cancer cells.
- In vivo studies revealed poor, non-displaceable tumor accumulation and rapid liver metabolism in the in ovo model.
Conclusions
- [carbonyl-<sup>11</sup>C]DPQ exhibits metabolic stability and specific binding in vitro.
- However, suboptimal tumor targeting and significant liver metabolism in vivo preclude its further development.
- No further animal studies in mammalian models were indicated based on these findings.
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