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.
OBJECTIVE
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
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.
Everitt
Sarah
S
Radiation Therapy Services, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Sarah.Everitt@petermac.org
Hicks
Rodney J
RJ
Ball
David
D
Kron
Tomas
T
Schneider-Kolsky
Michal
M
Walter
Tania
T
Binns
David
D
Mac Manus
Michael
M
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed / Q000379:methods
D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C002854:alovudine