In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification
Abstract
Prostate cancer is one of the most common malignancies worldwide, yet limited tools exist for prognostic risk stratification of the disease. Identification of new biomarkers representing intrinsic features of malignant transformation and development of prognostic imaging technologies are critical for improving treatment decisions and patient survival. In this study, we analyzed radical prostatectomy specimens from 422 patients with localized disease to define the expression pattern of methionine aminopeptidase II (MetAP2), a cytosolic metalloprotease that has been identified as a druggable target in cancer. MetAP2 was highly expressed in 54% of low-grade and 59% of high-grade cancers. Elevated levels of MetAP2 at diagnosis were associated with shorter time to recurrence. Controlled self-assembly of a synthetic small molecule enabled design of the first MetAP2-activated PET imaging tracer for monitoring MetAP2 activity in vivo. The nanoparticles assembled upon MetAP2 activation were imaged in single prostate cancer cells with post-click fluorescence labeling. The fluorine-18–labeled tracers successfully differentiated MetAP2 activity in both MetAP2-knockdown and inhibitor-treated human prostate cancer xenografts by micro-PET/CT scanning. This highly sensitive imaging technology may provide a new tool for noninvasive early-risk stratification of prostate cancer and monitoring the therapeutic effect of MetAP2 inhibitors as anticancer drugs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 26, 2021
- Source ID
- 10.1158/0008-5472.can-20-2969
Entities
People
- Bin Shen
- Chiyuan A. Zhang
- Christian A Kunder
- En-Chi Hsu
- Frederick T. Chin
- Guosheng Song
- James D Brooks
- Jessa B. Castillo
- Jianghong Rao
- Jinghang Xie
- Kaixiang Zhou
- Liyang Cui
- Meghan A Rice
- Min Chen
- Tanya Stoyanova
- Yunfeng Cheng
- Zixin Chen
Organizations
- Congressionally Directed Medical Research Programs
- National Cancer Institute
- National Institutes of Health
- Stanford University