Positron Emission Tomography Imaging of Poly–(Adenosine Diphosphate–Ribose) Polymerase 1 Expression in Breast Cancer: A Nonrandomized Clinical Trial
Mené sur 30 patientes atteintes d'un cancer primitif du sein de stade I à IV, cet essai évalue l'intérêt, pour prédire la cytotoxicité et l'efficacité des inhibiteurs de PARP, de mesurer in vivo le niveau d'expression de PARP-1 à l'aide d'une tomographie numérique par émission de positrons utilisant un inhibiteur de PARP radiomarqué
Clinical trial data demonstrate poly–(adenosine diphosphate–ribose) polymerase (PARP) inhibitor drug efficacy in individuals with BRCA1/2 pathogenic variants, but not all germline pathogenic variant carriers respond, and some without germline pathogenic variants also derive significant benefit. [18F]FluorThanatrace ([18F]FTT) is a radiolabeled PARP inhibitor that enables noninvasive quantification of PARP-1. In vitro data demonstrate that the level of PARP-1 correlates positively with cytotoxicity of PARP inhibitors and that PARP-1 expression is required for PARP inhibitor efficacy. In this prospective nonrandomized clinical trial, we report on PARP-1 positron emission tomography imaging using [18F]FTT in patients with breast cancer across a range of breast cancer phenotypes. These proof-of-concept results provide support for testing [18F]FTT as a method for measuring regional PARP-1 expression in breast cancer and as a potential functional biomarker for breast cancer PARP inhibitor response.
JAMA Oncology , résumé, 2019