Early evaluation of the effects of chemotherapy with longitudinal FDG small-animal PET in human testicular cancer xenografts: early flare response does not reflect refractory disease.
OBJECTIVE
We aimed to evaluate the usefulness of FDG PET in the early prediction of the effects of chemotherapy on human testicular cancer xenografts.


METHODS
Nude rats bearing subcutaneous human embryonal carcinoma xenografts received either cisplatin (5 mg/kg) or saline serum. Small-animal PET studies were performed on days 0, 2, 4 and 7 and compared to immunochemistry studies, flow cytometry studies and hexokinase assays.


RESULTS
Cisplatin treatment resulted in biphasic FDG uptake evolution: a peak was observed on day 2, followed by a marked decrease on day 7 despite an insignificant change in tumour volume. Similarly, a peak in cyclin A immunostaining was observed on days 2 and 4), followed by a significant decrease on day 7. Flow cytometry showed that the cyclin A peak was not related to increased cell proliferation but was due to a transient S and G(2)/M cell cycle arrest. A marked increase in cell apoptosis was observed from day 2 to day 7. GLUT-1 showed a significant decrease on day 7. Macrophagic infiltrate remained stable except for an increase observed on day 7. In control tumours, continuous growth was observed, all immunostaining markers remaining stable over time. Hexokinase activity was significantly lower on day 7 in treated tumours than in controls.


CONCLUSIONS
FDG PET may be useful in the early evaluation of treatment in patients with testicular cancer. In our model, a very early increased [(18)F]-FDG uptake was related to a transient cell cycle arrest and early stage apoptosis but did not reveal refractory disease.
Aide
Nicolas
N
Bioticla Unit, GRECAN, EA 1772, IFR 146 ICORE, Caen University, Caen, France. n.aide@baclesse.fr
Poulain
Laurent
L
Briand
Mélanie
M
Dutoit
Soizic
S
Allouche
Stéphane
S
Labiche
Alexandre
A
Ngo-Van Do
Aurélie
A
Nataf
Valérie
V
Batalla
Alain
A
Gauduchon
Pascal
P
Talbot
Jean-noël
JN
Montravers
Françoise
F
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D018236:Carcinoma, Embryonal / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000627:therapeutic use; D019925:Cyclin A / Q000378:metabolism; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D011923:Rats, Nude; D013736:Testicular Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019925:Cyclin A; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D002945:Cisplatin