Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography.
OBJECTIVE
3'-deoxy-3'-[18F]fluorothymidine positron emission tomography ([18F]FLT-PET) has been developed for imaging cell proliferation and findings correlate strongly with the Ki-67 labelling index in breast cancer. The aims of this pilot study were to define objective criteria for [18F]FLT response and to examine whether [18F]FLT-PET can be used to quantify early response of breast cancer to chemotherapy.


METHODS
Seventeen discrete lesions in 13 patients with stage II-IV breast cancer were scanned prior to and at 1 week after treatment with combination 5-fluorouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. The uptake at 90 min (SUV90) and irreversible trapping (Ki) of [18F]FLT were calculated for each tumour. The reproducibility of [18F]FLT-PET was determined in nine discrete lesions from eight patients who were scanned twice before chemotherapy. Clinical response was assessed at 60 days after commencing FEC.


RESULTS
All tumours showed [18F]FLT uptake and this was reproducible in serial measurements (SD of mean % difference=10.5% and 15.1%, for SUV90 and Ki, respectively; test-retest correlation coefficient>or=0.97). Six patients had a significant clinical response (complete or partial) at day 60; these patients also had a significant reduction in [18F]FLT uptake at 1 week. Decreases in Ki and SUV90 at 1 week discriminated between clinical response and stable disease (p=0.022 for both parameters). In three patients with multiple lesions there was a mixed [18F]FLT response in primary tumours and metastases. [18F]FLT response generally preceded tumour size changes.


CONCLUSIONS
[18F]FLT-PET can detect changes in breast cancer proliferation at 1 week after FEC chemotherapy.
Kenny
Laura
L
Imperial College London, and Hammersmith Hospital NHS Trust, London, UK.
Coombes
R Charles
RC
Vigushin
David M
DM
Al-Nahhas
Adil
A
Shousha
Sami
S
Aboagye
Eric O
EO
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D049109:Cell Proliferation; D003520:Cyclophosphamide / Q000008:administration & dosage; D015224:Dideoxynucleosides / Q000494:pharmacology*; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007700:Kinetics; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D019394:Ki-67 Antigen; D015251:Epirubicin; D003520:Cyclophosphamide; C002854:alovudine; D005472:Fluorouracil