Comparison of [18F]-tracers in various experimental tumor models by PET imaging and identification of an early response biomarker for the novel microtubule stabilizer patupilone.
OBJECTIVE
The suitability of [18F]FDG, [18F]FLT, [18F]FET, and [18F]FCH as non-invasive positron emission tomography (PET) biomarkers for monitoring response to chemotherapy was analyzed in various experimental tumor models.


METHODS
Tracer uptake into three syngeneic rodent tumor models and ten human xenograft models was evaluated using semiquantitative analysis of small-animal PET data. Murine RIF-1 fibrosarcomas and [18F]FLT were selected to monitor the effects of the novel cytotoxic patupilone.


RESULTS
Except [18F]FCH, all tracers provided good tumor visualization. Highest [18F]FDG uptake was identified in syngeneic tumors. Xenograft models, however, showed low [18F]FDG SUVs and were better visualized by [18F]FLT. Monitoring the effects of patupilone on [18F]FLT uptake in RIF-1 tumors revealed a significant decrease of tracer uptake after 24 h, which strongly negatively correlated with apoptosis.


CONCLUSIONS
[18F]FLT PET of experimental tumors is a viable complement to [18F]FDG for preclinical drug development. [18F]FLT may be an excellent biomarker for patupilone-induced apoptosis.
Ebenhan
T
T
Global Imaging Group, Novartis Institute of Biomedical Research, 4002 Basel, Switzerland.
Honer
M
M
Ametamey
S M
SM
Schubiger
P A
PA
Becquet
M
M
Ferretti
S
S
Cannet
C
C
Rausch
M
M
McSheehy
P M J
PM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002794:Choline / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D034261:Epothilones / Q000494:pharmacology*; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D014183:Transplantation, Heterologous; D050257:Tubulin Modulators / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D051598:Whole Body Imaging / Q000379:methods
D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D034261:Epothilones; D005462:Fluorine Radioisotopes; C493093:O-(18F)fluoromethyl-L-tyrosine; D019275:Radiopharmaceuticals; D050257:Tubulin Modulators; D019788:Fluorodeoxyglucose F18; D014443:Tyrosine; C514960:fluorocholine; D002794:Choline; C002854:alovudine; C093788:epothilone B