Your browser doesn't support javascript.
loading
In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification.
Xie, Jinghang; Rice, Meghan A; Chen, Zixin; Cheng, Yunfeng; Hsu, En-Chi; Chen, Min; Song, Guosheng; Cui, Liyang; Zhou, Kaixiang; Castillo, Jessa B; Zhang, Chiyuan A; Shen, Bin; Chin, Frederick T; Kunder, Christian A; Brooks, James D; Stoyanova, Tanya; Rao, Jianghong.
  • Xie J; Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
  • Rice MA; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, California.
  • Chen Z; Department of Chemistry, Stanford University, Stanford, California.
  • Cheng Y; Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
  • Hsu EC; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, California.
  • Chen M; Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
  • Song G; Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
  • Cui L; Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
  • Zhou K; Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
  • Castillo JB; Department of Radiology, Cyclotron and Radiochemistry Facility, Stanford University School of Medicine, Stanford, California.
  • Zhang CA; Department of Urology, Stanford University School of Medicine, Stanford, California.
  • Shen B; Department of Radiology, Cyclotron and Radiochemistry Facility, Stanford University School of Medicine, Stanford, California.
  • Chin FT; Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California.
  • Kunder CA; Department of Radiology, Cyclotron and Radiochemistry Facility, Stanford University School of Medicine, Stanford, California.
  • Brooks JD; Department of Urology, Stanford University School of Medicine, Stanford, California.
  • Stoyanova T; Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, California.
  • Rao J; Department of Urology, Stanford University School of Medicine, Stanford, California.
Cancer Res ; 81(9): 2510-2521, 2021 05 01.
Article en En | MEDLINE | ID: mdl-33637565
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.

SIGNIFICANCE:

This study defines MetAP2 as an early-risk stratifier for molecular imaging of aggressive prostate cancer and describes a MetAP2-activated self-assembly small-molecule PET tracer for imaging MetAP2 activity in vivo.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Transducción de Señal / Metionil Aminopeptidasas / Tomografía Computarizada por Tomografía de Emisión de Positrones Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Transducción de Señal / Metionil Aminopeptidasas / Tomografía Computarizada por Tomografía de Emisión de Positrones Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Año: 2021 Tipo del documento: Article