Preclinical and first-in-human-brain-cancer applications of [(18)F]poly (ADP-ribose) polymerase inhibitor PET/MR Journal Article
| Authors: | Young, R. J.; De Souza França, P. D.; Pirovano, G.; Piotrowski, A. F.; Nicklin, P. J.; Riedl, C. C.; Schwartz, J.; Bale, T. A.; Donabedian, P. L.; Kossatz, S.; Burnazi, E. M.; Roberts, S.; Lyashchenko, S. K.; Miller, A. M.; Moss, N. S.; Fiasconaro, M.; Zhang, Z.; Mauguen, A.; Reiner, T.; Dunphy, M. P. |
| Article Title: | Preclinical and first-in-human-brain-cancer applications of [(18)F]poly (ADP-ribose) polymerase inhibitor PET/MR |
| Abstract: | Background: We report preclinical and first-in-human-brain-cancer data using a targeted poly (ADP-ribose) polymerase 1 (PARP1) binding PET tracer, [18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment-related changes. Methods: We applied a glioma model in p53-deficient nestin/tv-a mice, which were injected with [18F]PARPi and then sacrificed 1 h post-injection for brain examination. We also prospectively enrolled patients with brain cancers to undergo dynamic [18F]PARPi acquisition on a dedicated positron emission tomography/magnetic resonance (PET/MR) scanner. Lesion diagnosis was established by pathology when available or by Response Assessment in Neuro-Oncology (RANO) or RANO-BM response criteria. Resected tissue also underwent PARPi-FL staining and PARP1 immunohistochemistry. Results: In a preclinical mouse model, we illustrated that [18F]PARPi crossed the blood-brain barrier and specifically bound to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [18F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment-related changes independent of blood-brain barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancerous than in noncancerous tissue. Specificity was also corroborated by blocking fluorescent tracer uptake with an excess unlabeled PARP inhibitor in patient cancer biospecimen. Conclusions: Although larger studies are necessary to confirm and further explore this tracer, we describe the promising performance of [18F]PARPi as a diagnostic tool to evaluate patients with brain cancers and possible treatment-related changes. © 2020 The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. |
| Keywords: | brain cancer; pet; parp1; pet/mr; [<sup>18</sup>f]parpi |
| Journal Title: | Neuro-Oncology Advances |
| Volume: | 2 |
| Issue: | 1 |
| ISSN: | 2632-2498 |
| Publisher: | Oxford University Press |
| Date Published: | 2020-01-01 |
| Start Page: | vdaa119 |
| Language: | English |
| DOI: | 10.1093/noajnl/vdaa119 |
| PROVIDER: | scopus |
| PMCID: | PMC7758909 |
| PUBMED: | 33392502 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Robert J. Young and Mark P. Dunphy -- Source: Scopus |
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