Polyethylene Glycol 3350 (PEG 3350) as a Practical Vehicle for Rapid Reconstitution of PARPi-FL Formulations for Clinical Use

Mol Imaging Biol. 2023 Apr;25(2):294-302. doi: 10.1007/s11307-022-01756-8. Epub 2022 Jul 26.

Abstract

PARPi-FL is a molecularly specific fluorescent agent that targets poly ADP-ribose polymerase 1, a DNA repair enzyme overexpressed in the nuclei of tumor cells. This imaging agent is being investigated in a clinical trial (NCT03085147) for the detection of oral cancer. The PARPi-FL mouthwash formulation currently being used in the phase I/II clinical trial comprises 1,000 nM of PARPi-FL dissolved first in 4.5 ml of polyethylene glycol (PEG) 300 and then in 9.5 ml of water. This formulation requires a 2-step process that can be cumbersome for routine clinical use. To minimize errors and simplify the formulation process, we have developed a new one-step formulation, which requires only the direct addition of water into a vial containing a mixture of the PARPi-FL and PEG 3350, which is also a powder. In a series of analytical and preclinical studies, we demonstrate that the new formulation of PARPi-FL is stable over 365 days, sustains its characteristics, and performs similar to the previous formulation. Moving forward, the new formulation of the PARPi-FL will be used for patients accrued in the phase II clinical trial.

Keywords: Clinical trial; New formulation; PARP1; PARPi-FL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Humans
  • Mouth Neoplasms*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Polyethylene Glycols

Substances

  • polyethylene glycol 3350
  • Poly(ADP-ribose) Polymerase Inhibitors
  • polyethylene glycol 300
  • Polyethylene Glycols