Imaging of acute heart-transplant rejection using 99m-Technetium labelled oligonucleotides against interleukin-2 mRNA in rats.
OBJECTIVE
Today, acute cardiac rejection is detected by endomyocardial biopsy, which harbours many risks. Thus, there is a necessity for less invasive methods. Since interleukin-2 (IL2) is over-expressed in acute graft rejection, we use radioactive DNA-fragments complementary to the mRNA of IL2 to detect graft rejection scintigraphically.


METHODS
In a rat model of acute graft rejection, the oligonucleotide sequence complementary to the mRNA of IL2 is labelled with 99m-Technetium and injected intravenously. Scintigraphic and Geiger-counter activity of the transplants are evaluated and correlated with the current rejection classification of the International Society for Heart and Lung Transplantation (ISHLT).


RESULTS
From the fourth postoperative day onwards, the scintigraphic images show a significant increase of radioactivity (p<0.05) in the rejected organs than in the accepted grafts. While scintigraphy is not significantly correlated with the standard rejections classification of the ISHLT, there is significant correlation between the ISHLT classification and radioactivity in the Geiger-counter analysis.


CONCLUSIONS
Radioactively labelled anti-sense-oligonucleotides against mRNA of IL2 may be a promising approach for the detection of acute transplant rejection in vivo.
Gierthmuehlen
Mortimer
M
Clinic for Nuclear Medicine, University of Schleswig Holstein, Campus Kiel, Germany. mortimer.gierthmuehlen@uniklinik-freiburg.de
Sommer
Per
P
Zuhayra
Maaz
M
Hedderich
Juergen
J
Jaenig
Ute
U
Faendrich
Fred
F
Henze
Eberhard
E
Kampen
Willm Uwe
WU
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000000981:diagnostic imaging*; D016027:Heart Transplantation; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000235:genetics; D011874:Radiometry; D011877:Radionuclide Imaging; D051381:Rats; D011917:Rats, Inbred Lew; D013667:Technetium
D015415:Biomarkers; D007376:Interleukin-2; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013667:Technetium