Evaluation of 3'-deoxy-3'-18F-fluorothymidine for monitoring tumor response to radiotherapy and photodynamic therapy in mice.
3'-Deoxy-3'-18F-fluorothymidine (18F-FLT) has been suggested as a new PET tracer for imaging tumor proliferation. We investigated the use of 18F-FLT to monitor the response of tumors to radiotherapy and photodynamic therapy (PDT) in mice.


METHODS
C3H/He mice bearing an SCCVII tumor were treated with single-dose x-ray irradiation of 20 Gy. Tumor uptake was examined for 18F-FLT, 3H-thymidine (3H-Thd), 18F-FDG, and 14C-deoxyglucose (14C-DG) at 6 h, 12 h, 24 h, 3 d, and 7 d after radiotherapy. BALB/c nu/nu mice bearing a HeLa tumor were treated with PDT. Tumor uptake was examined for the 4 tracers at 24 h after PDT. Expression of proliferating cell nuclear antigen (PCNA) was determined in untreated and treated tumors.


RESULTS
In the biodistribution study, considerable uptake of 18F-FLT was observed in both tumor types. Tumor volumes decreased to 39.3% +/- 22.4% at 7 d after radiotherapy. The PCNA labeling index was reduced in x-ray-irradiated tumors (control, 53.2% +/- 8.7%; 6 h, 38.5% +/- 5.3%; 24 h after radiotherapy, 36.8% +/- 5.3%). 18F-FLT uptake in tumor expressed as the percentage of the injected dose per gram of tumor (%ID/g) decreased significantly at 6 h and remained low until 3 d after radiotherapy (control, 9.7 +/- 1.2 %ID/g; 6 h, 5.9 +/- 0.4 %ID/g; 24 h, 6.1 +/- 1.3 %ID/g; 3 d after radiotherapy, 6.4 +/- 1.1 %ID/g). 18F-FDG uptake tended to gradually decrease but a significant decrease was found only at 3 d (control, 12.1 +/- 2.7 %ID/g; 6 h, 13.3 +/- 2.3 %ID/g; 24 h, 8.6 +/- 1.8 %ID/g; 3 d after radiotherapy, 6.9 +/- 1.2 %ID/g). PDT resulted in a reduction of the PCNA labeling index (control, 82.0% +/- 8.6%; 24 h after PDT, 13.5% +/- 12.7%). Tumor uptake of 18F-FLT decreased (control, 11.1 +/- 1.3 %ID/g; 24 h after PDT, 4.0 +/- 2.2 %ID/g), whereas 18F-FDG uptake did not decrease significantly after PDT (control, 3.5 +/- 0.6 %ID/g; 24 h after PDT, 2.3 +/- 1.1 %ID/g). Changes in the uptake of 18F-FLT and 18F-FDG were similar to those of 3H-Thd and 14C-DG, respectively.


CONCLUSIONS
In our model system, changes in 18F-FLT uptake after radiotherapy and PDT were correlated with those of 3H-Thd and the PCNA labeling index. The decrease in 18F-FLT uptake after treatments was more rapid or pronounced than that of 18F-FDG. Therefore, 18F-FLT may be a feasible PET tracer for monitoring response to therapy in oncology.
Department of Radiology, Hamamatsu University School of Medicine, Hamamatsu, Japan. masahiro@akiha.hama-med.ac.jp
Masahiro
M
Sugiyama
Harumi
H
Sakahara
Kengo
K
Sato
Norihiro
N
Harada
Dai
D
Fukumoto
Takeharu
T
Kakiuchi
Toru
T
Hirano
Eiji
E
Kohno
Hideo
H
Tsukada
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009928:Organ Specificity; D010778:Photochemotherapy / Q000379:methods; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011878:Radiotherapy / Q000379:methods; D014018:Tissue Distribution; D016896:Treatment Outcome
D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine