Comparison of the [18F]-FDG and [18F]-FLT PET Tracers in the Evaluation of the Preclinical Proton Therapy Response in Hepatocellular Carcinoma

Abstract

The main objective of the present study was to compare the 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]-FDG) and 3′-[ 18 F]fluoro-3′-deoxythymidine ([ 18 F]-FLT) PET imaging biomarkers for the longitudinal follow-up of small animal proton therapy studies in the context of hepatocellular carcinoma (HCC). ProceduresSK-HEP-1 cells were injected into NMRI nude mice to mimic human HCC. The behavior of [ 18 F]-FDG and [ 18 F]-FLT tumor uptake was evaluated after proton therapy procedures. The proton single-fraction doses were 5, 10 and 20 Gy, with a dose rate of 10 Gy/min. The experimental protocol consisted of 8 groups of 10 mice, each group experiencing a particular dose/radiotracer condition. A reference PET exam was performed on each mouse the day before the irradiation procedure, followed by PET exams every three days up to 16 days after irradiation. Results[ 18 F]-FDG uptake showed a linear dose-dependent increase in the first days after treatment (37%, p<0.05), while [ 18 F]-FLT uptake decreased in a dose-dependent manner (e.g 21% for 5Gy compared to 10 Gy, p=1.1e-2). At the later time point, [ 18 F]-FDG normalized activity showed an 85% decrease (p<0.01) for both 10 and 20 Gy doses and no variation for 5 Gy.Conversely, a significant 61% (p=0.002) increase was observed for [ 18 F]-FLT normalized activity at 5 Gy and no variation for higher doses. ConclusionWe showed that the use of the [ 18 F]-FDG and [ 18 F]-FLT radiolabeled molecules can provide useful and complementary information for longitudinal follow-up of small animal proton therapy studies in the context of HCC. [ 18 F]-FDG PET imaging enables a treatment monitoring 3 several days / weeks postirradiation. On the other hand, [ 18 F]-FLT could represent a good candidate to monitor the treatment few days postirradiation, in the context of hypo-fractioned and close irradiations planning. This opens new perspectives in terms of treatment efficacy verification depending on the irradiation scheme.

Beam Chopper and RF Kicker Systems for the TR24 Cyclotron Injection Line

“…The first one was a beam chopper on which a high voltage was commuted by means of a fast switch. This fast chopper was developed to control the time of irradiation of underskin tumors of mice with proton beams in the scope of the RPPET project [9] funded by the French National Institute of Cancer (INCA) [10].…”