Monitoring response to radiotherapy in human squamous cell cancer bearing nude mice: comparison of 2'-deoxy-2'-[18F]fluoro-D-glucose (FDG) and 3'-[18F]fluoro-3'-deoxythymidine (FLT).
OBJECTIVE
The uptake of 3'-[18F]fluoro-3'-deoxythymidine (FLT), a proliferation marker, was measured before and during fractionated radiotherapy to evaluate the potential of FLT-positron emission tomography (PET) imaging as an indicator of tumor response compared to 2'-deoxy-2'-[18F]fluoro-D-glucose (FDG).


METHODS
Nude mice bearing established human head and neck xenografts (HNX-OE; nu/nu mice) were locally irradiated (three fractions/week; 22 Gy) using a 150-kVp unit. Multiple FDG- and FLT-PET scans were acquired during treatment. Tumor volume was determined regularly, and tissue was analyzed for biomarkers involved in tracer uptake.


RESULTS
Both groups revealed a significant decline in tumor volume (P<0.01) compared to untreated tumors. For FDG as well as for FLT, a significant decline in retention was observed at day 4. For FLT, most significant decline in retention was observed at day 12; whereas, for FDG, this was already noted at day 4. Maximum decline in tumor-to-nontumor ratios (T/NT) for FDG and FLT was 42+/-18% and 49+/-16% (mean+/-SD), respectively. FLT uptake was higher then that of FDG. For FLT, statistical significant correlations were found for both tumor volume at baseline and at day 29 with T/NT and DeltaT/NT. All tumors demonstrated expression of glucose transporter-1, thymidine kinase-1, and hexokinase II. No differences were found for amount of tumor cells and necrosis at the end of treatment.


CONCLUSIONS
This new experimental in vivo model supports the promise of using FLT-PET, as with FDG-PET, to monitor response to external radiotherapy. This warrants further clinical studies to compare these two tracers especially in cancers treated with radiotherapy.
Molthoff
Carla F M
CF
Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007, Amsterdam, The Netherlands. cfm.molthoff@vumc.nl
Klabbers
Bianca M
BM
Berkhof
Johannes
J
Felten
Jasper T
JT
van Gelder
Marcelle
M
Windhorst
Albert D
AD
Slotman
Ben J
BJ
Lammertsma
Adriaan A
AA
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D015224:Dideoxynucleosides / Q000378:metabolism*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D011834:Radiation Monitoring / Q000379:methods*; D011836:Radiation Tolerance; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D015224:Dideoxynucleosides; D009363:Neoplasm Proteins; D019788:Fluorodeoxyglucose F18; C002854:alovudine