Dynamic PET imaging of tumor hypoxia using [F18]FRP170 in cancer patients

Abstract

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Objectives: [F18]FRP170, 1-(2-fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole, is a new PET tracer for imaging hypoxia. Non-invasive hypoxia imaging using PET has been sought for many years. [F18]FMISO has been widely used for hypoxia imaging, but has a low target-to-background ratio because of its high lipophilicity. [F18]FRP170 is designed as a more hydrophilic 2-nitroimidazole analog than [F18]FMISO. Therefore, we can expect better image contrast and faster clearance than with [F18]FMISO. Until now, we have reported experimental tumor imaging and human imaging in healthy volunteers using [F18]FRP170. Recently, we started clinical cancer imaging. But the optimal timing for tumor imaging using this tracer is unknown. In this study, we performed dynamic imaging in cancer patients and evaluated the changes of images with passage of time.

Methods: Three patients with primary lung cancer were enrolled with informed consent. Each patient received a nominal 185 MBq (5mCi) dose of [F18]FRP170 administered as a bolus intravenous injection in the arm. From just after injection, dynamic PET scans were performed for one or two hours using a dedicated PET scanner ( SET-2400W, Shimadzu Inc., Kyoto, Japan ). Emission scans (2D mode) were obtained for 2 min/frame (0-30 min) or 5 min/frame (after 30 min). Regions of interest were placed in the tumor, muscle and blood (aorta), and SUV analysis was performed. We evaluated time-SUV curves for tumor, muscle and blood. And we also calculated the tumor/blood ratio and tumor/muscle ratio.

Results: Time-SUV curves for tumor, muscle and blood showed the peaks within 5 min after injection. The blood showed the highest peak, and the tumor showed the second highest. After the peaks, each SUV decreased gradually. SUV of the blood dipped from that of the tumor around 10 min after injection. The muscle showed the lowest SUV consistently. The tumor/blood ratio showed slight elevation with time. The tumor/muscle ratio showed slight declination till around 50 min. After that, it showed slight elevation. The average SUVs at 60 min of tumor, muscle and blood were 1.35 ( range : 1.02-1.70 ), 1.04 ( 0.79-1.31 ) and 1.24 ( 1.14-1.35 ), respectively.

Conclusions: The initial rapid SUV changes of tumor, muscle and blood come to an end within 10 to 20 min after injection. The distribution of [F18]FRP170 becomes stable early. This may come from the high hydrophilicity of the tracer, and is thought to be one of the advantages of [F18]FRP170 over [F18]FMISO.