PT  - JOURNAL ARTICLE
AU  - Anne Roivainen
AU  - Tuula Tolvanen
AU  - Satu Salomäki
AU  - Gabor Lendvai
AU  - Irina Velikyan
AU  - Petri Numminen
AU  - Maria Välilä
AU  - Hannu Sipilä
AU  - Mats Bergström
AU  - Pirkko Härkönen
AU  - Harri Lönnberg
AU  - Bengt Långström
TI  - <sup>68</sup>Ga-Labeled Oligonucleotides for In Vivo Imaging with PET
DP  - 2004 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 347--355
VI  - 45
IP  - 2
4099  - http://jnm.snmjournals.org/content/45/2/347.short
4100  - http://jnm.snmjournals.org/content/45/2/347.full
SO  - J Nucl Med2004 Feb 01; 45
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.