Imaging of Cancer γ-Secretase Activity Using an Inhibitor-Based PET Probe.

ABSTRACT:

Purpose

Abnormal Notch signaling promotes cancer cell growth and tumor progression in various cancers. Targeting γ-secretase, a pivotal regulator in the Notch pathway, has yielded numerous γ-secretase inhibitors (GSIs) for clinical investigation in the last 2 decades. However, GSIs have demonstrated minimal success in clinical trials in part due to the lack of specific and precise tools to assess γ-secretase activity and its inhibition in vivo.

Experimental design

We designed an imaging probe based on GSI Semagacestat structure and synthesized the radioiodine-labeled analogues [¹³¹I]- or [¹²⁴I]-PN67 from corresponding trimethyl-tin precursors. Both membrane- and cell-based ligand-binding assays were performed using [¹³¹I]-PN67 to deter

SUBMITTER: Nie P 

PROVIDER: S-EPMC8610083 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature