A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Ga-68-labeled oligonucleotides for in vivo imaging with PET
Tekijät: Roivainen A, Tolvanen T, Salomaki S, Lendvai G, Velikyan I, Numminen P, Valila M, Sipila H, Bergstrom M, Harkonen P, Lonnberg H, Langstrom B
Kustantaja: SOC NUCLEAR MEDICINE INC
Julkaisuvuosi: 2004
Lehti:: Journal of Nuclear Medicine
Tietokannassa oleva lehden nimi: JOURNAL OF NUCLEAR MEDICINE
Lehden akronyymi: J NUCL MED
Vuosikerta: 45
Numero: 2
Aloitussivu: 347
Lopetussivu: 355
Sivujen määrä: 9
ISSN: 0161-5505
Tiivistelmä
The biologic evaluation in living rats of Ga-68-labeled oligonucleotides as imaging agents for PET is reported. Methods: Ga-68, 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 Ga-68-oligonucleotide. Blank studies were performed using (GaCl3)-Ga-68 or Ga-68-DOTA alone without oligonucleotide. The Ga-68-antisense oligonucleotide uptake in tumors was also compared with the F-18-FDG and Ga-68-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 Ga-68 and DOTA chelate. Intravenously injected Ga-68-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 Ga-68-oligonucleotide varied considerably with the nature of the oligonucleotide backbone. Conclusion: We conclude that Ga-68 labeling of oligonucleotides is a convenient approach for in vivo imaging and quantification of oligonucleotide biokinetics in living animals with PET.
The biologic evaluation in living rats of Ga-68-labeled oligonucleotides as imaging agents for PET is reported. Methods: Ga-68, 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 Ga-68-oligonucleotide. Blank studies were performed using (GaCl3)-Ga-68 or Ga-68-DOTA alone without oligonucleotide. The Ga-68-antisense oligonucleotide uptake in tumors was also compared with the F-18-FDG and Ga-68-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 Ga-68 and DOTA chelate. Intravenously injected Ga-68-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 Ga-68-oligonucleotide varied considerably with the nature of the oligonucleotide backbone. Conclusion: We conclude that Ga-68 labeling of oligonucleotides is a convenient approach for in vivo imaging and quantification of oligonucleotide biokinetics in living animals with PET.
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