Ultrasmall [64Cu]Cu nanoclusters for targeting orthotopic lung tumors using accurate positron emission tomography imaging

Fuping Gao, Pengju Cai, Wenjiang Yang, Jingquan Xue, Liang Gao, Ru Liu, Yaling Wang, Yawei Zhao, Xiao He, Lina Zhao, Guodong Huang, Fasheng Wu, Yuliang Zhao, Zhifang Chai, Xueyun Gao

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


Positron emission tomography (PET) imaging has received special attention owing to its higher sensitivity, temporal resolution, and unlimited tissue penetration. The development of tracers that target specific molecules is therefore essential for the development and utility of clinically relevant PET procedures. However, 64Cu as a PET imaging agent generally has been introduced into biomaterials through macrocyclic chelators, which may lead to the misinterpretation of PET imaging results due to the detachment and transchelation of 64Cu. In this study, we have developed ultrasmall chelator-free radioactive [64Cu]Cu nanoclusters using bovine serum albumin (BSA) as a scaffold for PET imaging in an orthotopic lung cancer model. We preconjugated the tumor target peptide luteinizing hormone releasing hormone (LHRH) to BSA molecules to prepare [64Cu]CuNC@BSA-LHRH. The prepared [64Cu]Cu nanoclusters showed high radiolabeling stability, ultrasmall size, and rapid deposition and diffusion into tumor, as well as predominantly renal clearance. [64Cu]CuNC@BSA-LHRH showed 4 times higher tumor uptake compared with that of [64Cu]CuNC@BSA by analyzing the 64Cu radioactivity of tissues via gamma counting. The PET imaging using [64Cu]Cu nanoclusters as tracers showed more sensitive, accurate, and deep penetration imaging of orthotopic lung cancer in vivo compared with near-infrared fluorescence imaging. The nanoclusters provide biomedical research tools for PET molecular imaging.

Original languageEnglish (US)
Pages (from-to)4976-4986
Number of pages11
JournalACS Nano
Issue number5
StatePublished - May 26 2015


  • copper nanoclusters
  • luteinizing hormone releasing hormone
  • orthotopic lung tumor
  • positron emission tomography imaging
  • tumor target

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)


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