Validation of sv2a-targeted pet imaging for noninvasive assessment of neuroendocrine differentiation in prostate cancer

Bing Guan, Ning Zhou, Cheng Yang Wu, Songye Li, Yu An Chen, Sashi Debnath, Mia Hofstad, Shihong Ma, Ganesh V. Raj, Dalin He, Jer Tsong Hsieh, Yiyun Huang, Guiyang Hao, Xiankai Sun

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroendocrine prostate cancer (NEPC) is an aggressive and lethal variant of prostate cancer (PCa), and it remains a diagnostic challenge. Herein we report our findings of using synaptic vesicle glycoprotein 2 isoform A (SV2A) as a promising marker for positron emission tomography (PET) imaging of neuroendocrine differentiation (NED). The bioinformatic analyses revealed an amplified SV2A gene expression in clinical samples of NEPC versus castration-resistant PCa with adenocarcinoma characteristics (CRPC-Adeno). Importantly, significantly upregulated SV2A protein levels were found in both NEPC cell lines and tumor tissues. PET imaging studies were carried out in NEPC xenograft models with18F-SynVesT-1. Although18F-SynVesT-1 is not a cancer imaging agent, it showed a significant uptake level in the SV2A+ tumor (NCI-H660: 0.70 ± 0.14 %ID/g at 50–60 min p.i.). The SV2A blockade resulted in a significant reduction of tumor uptake (0.25 ± 0.03 %ID/g, p = 0.025), indicating the desired SV2A imaging specificity. Moreover, the comparative PET imaging study showed that the DU145 tumors could be clearly visualized by18F-SynVesT-1 but not68Ga-PSMA-11 nor68Ga-DOTATATE, further validating the role of SV2A-targeted imaging for noninvasive assessment of NED in PCa. In conclusion, we demonstrated that SV2A, highly expressed in NEPC, can serve as a promising target for noninvasive imaging evaluation of NED.

Original languageEnglish (US)
Article number13085
JournalInternational journal of molecular sciences
Volume22
Issue number23
DOIs
StatePublished - Dec 1 2021

Keywords

  • F-SynVesT-1
  • Neuroendocrine differentiation (NED)
  • Neuroendocrine prostate cancer (NEPC)
  • Positron emission tomography (PET)
  • Synaptic vesicle glycoprotein 2 isoform A (SV2A)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'Validation of sv2a-targeted pet imaging for noninvasive assessment of neuroendocrine differentiation in prostate cancer'. Together they form a unique fingerprint.

Cite this