68Ga-Labeled Oligonucleotides for In Vivo Imaging with PET

Journal of Nuclear Medicine

Gabor Lendvai¹  Anne Roivainen¹  Satu Salomäki¹  Petri Numminen¹  Tuula Tolvanen¹  Mats Bergström¹  Hannu Sipilä¹  Maria Välilä¹  Harri Lönnberg¹  Pirkko Härkönen¹  Irina Velikyan¹  Bengt Långström¹ 

关键词: ⁶⁸Ga;    oligonucleotides;    in vivo imaging;    PET;    biokinetics;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 oligonucleotidesthat 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.

【 授权许可】

Unknown