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

Purpose: The main objective of the present study was to compare the 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]-FDG) and 3'-[¹⁸F]fluoro-3'-deoxythymidine ([¹⁸F]-FLT) PET imaging biomarkers for the longitudinal follow-up of small animal proton therapy studies in the context of hepatocellular carcinoma (HCC).

Procedures: SK-HEP-1 cells were injected into NMRI nude mice to mimic human HCC. The behavior of [¹⁸F]-FDG and [¹⁸F]-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 3 days up to 16 days after irradiation.

Results: [¹⁸F]-FDG uptake showed a linear dose-dependent increase in the first days after treatment (37%, p < 0.05), while [¹⁸F]-FLT uptake decreased in a dose-dependent manner (e.g., 21% for 5 Gy compared to 10 Gy, p = 1.1e-2). At the later time point, [¹⁸F]-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 [¹⁸F]-FLT normalized activity at 5 Gy and no variation for higher doses.

Conclusion: We showed that the use of the [¹⁸F]-FDG and [¹⁸F]-FLT radiolabeled molecules can provide useful and complementary information for longitudinal follow-up of small animal proton therapy studies in the context of HCC. [¹⁸F]-FDG PET imaging enables a treatment monitoring several days/weeks postirradiation. On the other hand, [¹⁸F]-FLT could represent a good candidate to monitor the treatment few days postirradiation, in the context of hypo-fractioned and close irradiation planning. This opens new perspectives in terms of treatment efficacy verification depending on the irradiation scheme.