Imaging cellular proliferation during chemo-radiotherapy: a pilot study of serial 18F-FLT positron emission tomography/computed tomography imaging for non-small-cell lung cancer

Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1098-104. doi: 10.1016/j.ijrobp.2008.12.039. Epub 2009 Apr 20.

Abstract

Purpose: To establish whether (18)F-3'-deoxy-3'-fluoro-L-thymidine ((18)F-FLT) can monitor changes in cellular proliferation of non-small-cell lung cancer (NSCLC) during radical chemo-radiotherapy (chemo-RT).

Methods and materials: As part of a prospective pilot study, 5 patients with locally advanced NSCLC underwent serial (18)F-FLT positron emission tomography (PET)/computed tomography (CT) scans during treatment. Baseline (18)F-FLT PET/CT scans were compared with routine staging (18)F-FDG PET/CT scans. Two on-treatment (18)F-FLT scans were performed for each patient on Days 2, 8, 15 or 29, providing a range of time points for response assessment.

Results: In all 5 patients, baseline lesional uptake of (18)F-FLT on PET/CT corresponded to staging (18)F-FDG PET/CT abnormalities. (18)F-FLT uptake in tumor was observed on five of nine (55%) on-treatment scans, on Days 2, 8 and 29, but not Day 15. A "flare" of (18)F-FLT uptake in the primary tumor of one case was observed after 2 Gy of radiation (1.22 x baseline). The remaining eight on-treatment scans demonstrated a mean reduction in (18)F-FLT tumor uptake of 0.58 x baseline. A marked reduction of (18)F-FLT uptake in irradiated bone marrow was observed for all cases. This reduction was observed even after only 2 Gy, and all patients demonstrated a complete absence of proliferating marrow after 10 Gy.

Conclusions: This proof of concept study indicates that (18)F-FLT uptake can monitor the distinctive biologic responses of epithelial cancers and highly radiosensitive normal tissue changes during radical chemo-RT. Further studies of (18)F-FLT PET/CT imaging during therapy may suggest that this tracer is useful in developing response-adapted RT for NSCLC.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Cell Proliferation*
  • Combined Modality Therapy
  • Dideoxynucleosides* / pharmacokinetics
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Humans
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Pilot Projects
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals* / pharmacokinetics
  • Tomography, X-Ray Computed / methods

Substances

  • Dideoxynucleosides
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • alovudine