18F-RP-170

A novel [18F]FRP-170 injection for imaging hypoxia by PET was developed for clinical use. The preparation was based on the simple on-column basic-hydrolysis and the whole procedure was automated by detecting He flow change for transferring and evaporating liquids. [18F]FRP-170 was prepared in around 15-20% decay-corrected radiochemical yield within 60 min and stable in saline for more than 6 hr. Radiochemical purity was over 99% and specific activity at EOS was 40-60 GBq/micromol. The radiation-absorbed dose to the whole body was estimated to be 1.0 mSv/185 MBq. The [18F]FRP-170 injection proved to be suitable for clinical use without acute toxicity or mutagenicity.

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%.

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.

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.