[18F]-3'Deoxy-3'-fluorothymidine positron emission tomography and breast cancer response to docetaxel.
OBJECTIVE
To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [(18)F]-3'deoxy-3'-fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer.


METHODS
This was a prospective unblinded study in 20 patients with American Joint Committee on Cancer (AJCC) stage II-IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan 2 weeks after initiating the first or second cycle of docetaxel. PET variables were compared with anatomic response midtherapy (after 3 cycles).


RESULTS
Average and maximum tumor standardized uptake values at 60 minutes (SUV(60,av) and SUV(60,max)) normalized to body surface area ranged between 1.7 and 17.0 and 5.6 and 26.9 × 10(-5) m(2)/mL, respectively. Docetaxel treatment resulted in a significant decrease in FLT uptake (P = 0.0003 for SUV(60,av) and P = 0.0002 for SUV(60,max)). Reduction in tumor SUV(60,av) was associated with target lesion size changes midtherapy (Pearson R for SUV(60,av) = 0.64; P = 0.004) and predicted midtherapy target lesion response (0.85 sensitivity and 0.80 specificity). Decreases in SUV(60,av) in responders were due, at least in part, to reduced net intracellular trapping of FLT (rate constant, K(i)). Docetaxel significantly reduced K(i) by 51.1% (±28.4%, P = 0.0009).


CONCLUSIONS
Changes in tumor proliferation assessed by FLT-PET early after initiating docetaxel chemotherapy can predict lesion response midtherapy with good sensitivity warranting prospective trials to assess the ability to stop therapy in the event of non-FLT-PET response.
Departments of Surgery and Cancer, Neuroscience, and Nuclear Medicine, Imperial College London and Imperial College Healthcare NHS Trust, Hammersmith and Charing Cross Hospitals, London, United Kingdom.
Kaiyumars B
KB
Contractor
Laura M
LM
Kenny
Justin
J
Stebbing
Lula
L
Rosso
Rizvana
R
Ahmad
Jimmy
J
Jacob
Amarnath
A
Challapalli
Federico
F
Turkheimer
Adil
A
Al-Nahhas
Rohini
R
Sharma
R Charles
RC
Coombes
Eric O
EO
Aboagye
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D043823:Taxoids; D000077143:Docetaxel; C002854:alovudine