Imaging of ischemic but viable myocardium using a new 18F-labeled 2-nitroimidazole analog, 18F-FRP170.
RP170, 1-(2-hydroxy-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole, is a new hypoxic radiosensitizer. We recently succeeded in labeling this compound with 18F to make 18F-FRP170, 1-(2-fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole. In this study, we attempted to visualize the ischemic but viable myocardium of rats as hot-spot images using 18F-FRP170. We also compared the distribution of 18F-FRP170 with myocardial perfusion, fatty acid metabolism, and glucose metabolism.


METHODS
In open-chest rats, the left coronary artery was ligated to make an ischemic myocardial model. We evaluated the myocardial accumulation of radiotracers by the double-tracer autoradiography technique. 14C-Iodoantipyrine (IAP), 125I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP), and 14C-deoxyglucose (DG) were used as markers of myocardial perfusion, fatty acid metabolism, and glucose metabolism, respectively. Approximately 80 small circular regions of interest were placed throughout the left ventricular wall of the midventricular level section. The uptake in each region of interest was expressed as the percentage uptake of the average count in the remote area. We then defined the 18F-FRP170 high-uptake area (H-FRP) as that area where the percentage of FRP was >120% and the 18F-FRP170 low-uptake area (L-FRP) as that area where the percentage of FRP was <80%.


RESULTS
On the 18F-FRP170 image of the ischemic myocardium, there was a low-uptake area in the center, which was bounded by a high-uptake area. The percentages of IAP in the H-FRP and the L-FRP were 48.5% +/- 5.8% and 2.2% +/- 0.2%, respectively; the percentages of BMIPP in the H-FRP and the L-FRP were 46.8% +/- 3.1% and 4.3% +/- 0.4%, respectively; and the percentages of DG in the H-FRP and the L-FRP were 107.0% +/- 6.8% and 4.3% +/- 0.4%, respectively. In diabetic rats, the percentages of DG in the H-FRP and the L-FRP were 407.7% +/- 14.9% and 72.5% +/- 5.0%, respectively, but the remote area on the DG image was insufficiently visualized. Histologic data using 2,3,5-triphenyltetrazolium chloride staining suggest that the high-uptake areas on 18F-FRP170 images reflect ischemic but viable myocardium.


CONCLUSIONS
We succeeded in visualizing the ischemic but viable myocardium as a hot spot on the 18F-FRP170 image. 18F-FRP170 can be expected to provide important information for determining the necessity of coronary intervention in ischemic heart disease patients, including diabetic patients.
Kaneta
Tomohiro
T
Department of Radiology, Tohoku University, Sendai, Japan.
Takai
Yoshihiro
Y
Kagaya
Yutaka
Y
Yamane
Yuriko
Y
Wada
Hiroaki
H
Yuki
Masahiro
M
Iwata
Ren
R
Tsujitani
Michihiko
M
Takahashi
Shoki
S
Yamada
Shogo
S
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives*; D001345:Autoradiography; D002250:Carbon Radioisotopes; D003847:Deoxyglucose; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging; D005227:Fatty Acids / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000000981:diagnostic imaging*; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D009705:Nucleosides / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D009593:Nitroimidazoles; D009705:Nucleosides; D019275:Radiopharmaceuticals; C049338:iodofiltic acid; C060996:RP 170; D003847:Deoxyglucose; D005947:Glucose; D000983:Antipyrine; C008135:iodoantipyrine