RT Journal Article SR Electronic T1 68Ga-Labeled Oligonucleotides for In Vivo Imaging with PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 347 OP 355 VO 45 IS 2 A1 Anne Roivainen A1 Tuula Tolvanen A1 Satu Salomäki A1 Gabor Lendvai A1 Irina Velikyan A1 Petri Numminen A1 Maria Välilä A1 Hannu Sipilä A1 Mats Bergström A1 Pirkko Härkönen A1 Harri Lönnberg A1 Bengt Långström YR 2004 UL http://jnm.snmjournals.org/content/45/2/347.abstract AB 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.