C-X-C Chemokine Receptor Type 4-Targeted Imaging in Glioblastoma Multiforme Using 64Cu-Radiolabeled Ultrasmall Gold Nanoclusters

Xiaohui Zhang, Lisa Detering, Deborah Sultan, Gyu Seong Heo, Hannah Luehmann, Sara Taylor, Ankur Choksi, Joshua B. Rubin, Yongjian Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary malignant brain cancer in adults, and it carries a poor prognosis. Despite the current multimodality treatment, including surgery, radiation, and chemotherapy, the overall survival is still poor. Neurooncological imaging plays an important role in the initial diagnosis and prediction of the treatment response of GBM. Positron emission tomography (PET) imaging using radiotracers that target disease-specific hallmarks, which are both noninvasive and specific, has drawn much attention. C-X-C chemokine receptor 4 (CXCR4) plays an important role in neoangiogenesis and vasculogenesis, and, moreover, it is reported to be overexpressed in GBM, which is associated with poor patient survival; thus, CXCR4 can be an ideal candidate for PET imaging of GBM. Nanomaterials, which possess multifunctional capabilities, effective drug delivery, and favorable pharmacokinetics, are now being applied to improve the diagnosis and therapy of the most difficult-to-treat cancers. Herein, we engineered an ultrasmall, renal-clearable gold nanoclusters intrinsically radiolabeled with 64Cu (64Cu-AuNCs-FC131) for targeted PET imaging of CXCR4 in a U87 intracranial GBM mouse model. These targeted nanoclusters demonstrated specific binding to U87 cells with minimal cytotoxicity. The in vivo biodistribution showed favorable pharmacokinetics and efficient renal clearance. PET/computed tomography imaging of the U87 model revealed the effective delivery of 64Cu-AuNCs-FC131 into the tumors. In vivo toxicity studies demonstrated insignificant safety concerns at various dosages, indicating its potential as a useful platform for GBM imaging and drug delivery.

Original languageEnglish
Pages (from-to)235-242
Number of pages8
JournalACS Applied Bio Materials
Volume5
Issue number1
DOIs
StatePublished - Jan 17 2022

Keywords

  • C-X-C chemokine receptor type4
  • FC131 peptide
  • glioblastoma multiforme
  • nanoclusters
  • positron emission tomography

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