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68Ga-labeled oligonucleotides for in vivo imaging with PET

På svenska

Author

  • Anne Roivainen
  • Tuula Tolvanen
  • Satu Salomäki
  • Gabor Lendvai
  • Irina Velikyan
  • Petri Numminen
  • Maria Välilä
  • Hannu Sipilä
  • Mats Bergström
  • Pirkko Härkönen
  • Harri Lönnberg
  • Bengt Långström
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Summary, in English

The biologic evaluation in living rats of 68Ga-labeled oligonucleotides as imaging agents for PET is reported. Methods: 68Ga, a positron-emitting radionuclide (half-life, 68 min), along with a macrocyclic chelating agent, 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), was used for labeling of antisense oligonucleotides targeting activated human K-ras oncogene. The biologic properties of 3 different forms of the oligonucleotides—that is, 2'-deoxyphosphodiester (PO), 2'-deoxyphosphorothioate (PS), and 2'-O-methyl phosphodiester (OMe)—were studied first. The biodistribution and biokinetics were evaluated in vivo in athymic rats, each bearing a tumor of A549 cells, containing K-ras point mutation in codon 12, and a tumor of BxPC-3 cells, containing wild-type K-ras. Dynamic PET imaging lasting up to 2 h was performed immediately after intravenous injection of 68Ga-oligonucleotide. Blank studies were performed using 68GaCl3 or 68Ga-DOTA alone without oligonucleotide. The 68Ga-antisense oligonucleotide uptake in tumors was also compared with the 18F-FDG and 68Ga-sense oligonucleotide uptakes. In addition, oligonucleotide binding to human plasma proteins and to human albumin was examined by means of ultrafiltration. Results: The oligonucleotides can be stably labeled with 68Ga and DOTA chelate. Intravenously injected 68Ga-oligonucleotides of 17-mer length revealed high-quality PET images, allowing quantification of the biokinetics in major organs and in tumors. The biodistribution and biokinetics of intravenously administered 68Ga-oligonucleotide varied considerably with the nature of the oligonucleotide backbone. Conclusion: We conclude that 68Ga labeling of oligonucleotides is a convenient approach for in vivo imaging and quantification of oligonucleotide biokinetics in living animals with PET.

Publishing year

2004

Language

English

Pages

347-355

Publication/Series

Journal of Nuclear Medicine

Volume

45

Issue

2

Document type

Journal article

Publisher

Society of Nuclear Medicine

Topic

  • Cancer and Oncology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0161-5505