[64Cu]NOTA-pentixather enables high resolution PET imaging of CXCR4 expression in a preclinical lymphoma model

Andreas Poschenrieder, Margret Schottelius, Theresa Osl, Markus Schwaiger, Hans Jürgen Wester

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8 Scopus citations


Background: The chemokine receptor 4 (CXCR4) is an important molecular target for both visualization and therapy of tumors. The aim of the present study was the synthesis and preclinical evaluation of a64Cu-labeled, CXCR4-targeting peptide for positron emission tomography (PET) imaging of CXCR4 expression in vivo. Methods: For this purpose, 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), or 1,4,7-triazacyclononane-triacetic acid (NOTA) was conjugated to the highly affine CXCR4-targeting pentixather scaffold. Affinities were determined using Jurkat T-lymphocytes in competitive binding assays employing [125I]FC131 as the radioligand. Internalization and efflux studies of [64Cu]NOTA-pentixather were performed in chem-1 cells, stably transfected with hCXCR4. The stability of the tracer was evaluated in vitro and in vivo. Small-animal PET and biodistribution studies at different time points were performed in Daudi lymphoma-bearing severe combined immunodeficiency (SCID) mice. Results: [64Cu]NOTA-pentixather was rapidly radiolabeled at 60 °C with high radiochemical yields ≥90% and purities >99%. [64Cu]NOTA-pentixather offered the highest affinity of the evaluated peptides in this study (IC50 = 14.9 ± 2.1 nM), showed efficient CXCR4-targeting in vitro and was stable in blood and urine with high resistance to transchelation in ethylenediaminetetraacetic acid (EDTA) challenge studies. Due to the enhanced lipophilicity of [64Cu]NOTA-pentixather (logP = -1.2), biodistribution studies showed some nonspecific accumulation in the liver and intestines. However, tumor accumulation (13.1 ± 1.5% ID/g, 1.5 h p.i.) was CXCR4-specific and higher than in all other organs and resulted in high resolution delineation of Daudi tumors in PET/CT images in vivo. Conclusions: [64Cu]NOTA-pentixather was fast and efficiently radiolabeled, showed effective CXCR4-targeting, high stability in vitro and in vivo and resulted in high resolution PET/CT images accompanied with a suitable biodistribution profile, making [64Cu]NOTA-pentixather a promising tracer for future application in humans.

Original languageEnglish
Article number2
JournalEJNMMI Radiopharmacy and Chemistry
Issue number1
StatePublished - 1 Dec 2017


  • CXCR4
  • Cancer
  • Cu
  • GPCR
  • NOTA
  • PET
  • Pentapeptide
  • Radiopharmaceutical
  • Theranostic
  • Tracer


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