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

Mol Imaging Biol. 2021 Oct;23(5):724-732. doi: 10.1007/s11307-021-01602-3. Epub 2021 Apr 13.

Abstract

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.

Keywords: Hepatocellular carcinoma; Longitudinal study; PET; Preclinical studies; Proton therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / diagnostic imaging
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / therapy
  • Dideoxynucleosides* / chemistry
  • Dideoxynucleosides* / pharmacokinetics
  • Disease Models, Animal
  • Female
  • Fluorodeoxyglucose F18* / chemistry
  • Fluorodeoxyglucose F18* / pharmacokinetics
  • Liver Neoplasms* / diagnostic imaging
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / therapy
  • Mice
  • Mice, Nude
  • Positron-Emission Tomography*
  • Proton Therapy

Substances

  • Dideoxynucleosides
  • Fluorodeoxyglucose F18
  • alovudine