[18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response

Hanwen Zhang; Diane Abou; Peng Lu; Abbie Meghan Hasson; Alexandria Villmer; Nadia Benabdallah; Wen Jiang; David Ulmert; Sean Carlin; Buck E Rogers; Norman F Turtle; Michael R McDevitt; Brian Baumann; Brian W Simons; Farrokh Dehdashti; Dong Zhou; Daniel L J Thorek

doi:10.1038/s41598-022-17460-0

[¹⁸F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response

Sci Rep. 2022 Jul 29;12(1):13034. doi: 10.1038/s41598-022-17460-0.

Authors

Hanwen Zhang^{1

2

3}, Diane Abou^{1

2

4}, Peng Lu^{1

2

5}, Abbie Meghan Hasson^{1

2

5}, Alexandria Villmer^{1

2}, Nadia Benabdallah^{1

2}, Wen Jiang^{2

6}, David Ulmert^{7

8}, Sean Carlin⁹, Buck E Rogers^{2

10}, Norman F Turtle¹, Michael R McDevitt¹¹, Brian Baumann^{2

10}, Brian W Simons¹², Farrokh Dehdashti^{1

3}, Dong Zhou¹³, Daniel L J Thorek^{14

15

16

17}

Affiliations

¹ Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., Campus, Box 8225, St. Louis, MO, 63110, USA.
² Program in Quantitative Molecular Therapeutics, Washington University School of Medicine, St. Louis, MO, USA.
³ Oncologic Imaging Program, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
⁴ Radiology Cyclotron Facility, Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA.
⁵ Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
⁶ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁷ Johnsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
⁸ Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA.
⁹ Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁰ Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
¹¹ Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹² Center for Comparative Medicine, Baylor College of Medicine, Houston, TX, USA.
¹³ Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., Campus, Box 8225, St. Louis, MO, 63110, USA. [email protected].
¹⁴ Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., Campus, Box 8225, St. Louis, MO, 63110, USA. [email protected].
¹⁵ Program in Quantitative Molecular Therapeutics, Washington University School of Medicine, St. Louis, MO, USA. [email protected].
¹⁶ Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA. [email protected].
¹⁷ Oncologic Imaging Program, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. [email protected].

Abstract

The growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways-such as those induced by irradiation. Here, we used a third-generation PARP1-specific radiotracer, [¹⁸F]-PARPZ, to delineate castrate resistant prostate cancer xenografts. Following treatment with the clinically applied [²²⁵Ac]-PSMA-617, positron emission tomography was performed and correlative autoradiography and histology acquired. [¹⁸F]-PARPZ was able to distinguish treated from control (saline) xenografts by increased uptake. Kinetic analysis of tracer accumulation also suggests that the localization of the agent to sites of increased PARP-1 expression is a consequence of DNA damage response. Together, these data support expanded investigation of [¹⁸F]-PARPZ to facilitate clinical translation in the ⍺-therapy space.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Alpha Particles / therapeutic use
Fluorine Radioisotopes*
Humans
Kinetics
Male
Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
Positron-Emission Tomography / methods
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / metabolism
Prostatic Neoplasms* / radiotherapy
Tomography, X-Ray Computed

Substances

Fluorine Radioisotopes
Poly(ADP-ribose) Polymerase Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding