Folate-PEG-NOTA-Al18F: A New Folate Based Radiotracer for PET Imaging of Folate Receptor-Positive Tumors

Qingshou Chen, Xiangjun Meng, Paul McQuade, Daniel Rubins, Shu An Lin, Zhizhen Zeng, Hyking Haley, Patricia Miller, Dinko González Trotter, Philip S. Low

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The folate receptor (FR) has been established as a promising target for imaging and therapy of cancer (FR-α), inflammation, and autoimmune diseases (FR-β). Several folate based PET radiotracers have been reported in the literature, but an 18F-labeled folate-PET imaging agent with optimal properties for clinical translation is still lacking. In the present study, we report the design and preclinical evaluation of folate-PEG12-NOTA-Al18F (1), a new folate-PET agent with improved potential for clinical applications. Radiochemical synthesis of 1 was achieved via a one-pot labeling process by heating folate-PEG12-NOTA in the presence of in situ prepared Al18F for 15 min at 105 °C, followed by HPLC purification. Specific binding of 1 to FR was evaluated on homogenates of KB (FR-positive) and A549 (FR-deficient) tumor xenografts in the presence and absence of excess folate. In vivo tumor imaging with folate-PEG12-NOTA-Al18F was compared to imaging with 99mTc-EC20 using nu/nu mice bearing either KB or A549 tumor xenografts. Specific accumulation of 1 in tumor and other tissues was assessed by high-resolution micro-PET and ex vivo biodistribution in the presence and absence of excess folate. Radiosynthesis of 1 was accomplished within -35 min, affording pure radiotracer 1 in 8.4 ± 1.3% (decay corrected) radiochemical yield with 100% radiochemical purity after HPLC purification and a specific activity of 35.8 ± 15.3 GBq/mmol. Further in vitro and in vivo examination of 1 demonstrated highly specific FR-mediated uptake in FR+ tumor, with Kd of -0.4 nM (KB), and reduced accumulation in liver. Given its facile preparation and improved properties, the new radiotracer, folate-PEG12-NOTA-Al18F (1), constitutes a promising tool for identification and classification of patients with FR overexpressing cancers.

Original languageEnglish (US)
Pages (from-to)4353-4361
Number of pages9
JournalMolecular pharmaceutics
Issue number12
StatePublished - Dec 4 2017


  • AlF-NOTA
  • F-PET imaging
  • cancer imaging
  • folate conjugate
  • folate receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


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