Predicting chemotherapy response to paclitaxel with 18F-Fluoropaclitaxel and PET.
Paclitaxel is used as a chemotherapy drug for the treatment of various malignancies, including breast, ovarian, and lung cancers. To evaluate the potential of a noninvasive prognostic tool for specifically predicting the resistance of tumors to paclitaxel therapy, we examined the tumoral uptake of (18)F-fluoropaclitaxel ((18)F-FPAC) in mice bearing human breast cancer xenografts by using small-animal-dedicated PET and compared (18)F-FPAC uptake with the tumor response to paclitaxel treatment.


METHODS
PET data were acquired after tail vein injection of approximately 9 MBq of (18)F-FPAC in anesthetized nude mice bearing breast cancer xenografts. Tracer uptake in reconstructed images was quantified by region-of-interest analyses and compared with the tumor response, as measured by changes in tumor volume, after treatment with paclitaxel.


RESULTS
Mice with tumors that progressed demonstrated lower tumoral uptake of (18)F-FPAC than mice with tumors that did not progress or that regressed (r = 0.55, P < 0.02; n = 19), indicating that low (18)F-FPAC uptake was a significant predictor of chemoresistance. Conversely, high (18)F-FPAC uptake predicted tumor regression. This relationship was found for mice bearing xenografts from cell lines selected to be either sensitive or intrinsically resistant to paclitaxel in vitro.


CONCLUSIONS
PET data acquired with (18)F-FPAC suggest that this tracer holds promise for the noninvasive quantification of its distribution in vivo in a straightforward manner. In combination with approaches for examining other aspects of resistance, such quantification could prove useful in helping to predict subsequent resistance to paclitaxel chemotherapy of breast cancer.
Hsueh
Wei-Ann
WA
Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-6942, USA.
Kesner
Amanda L
AL
Gangloff
Anne
A
Pegram
Mark D
MD
Beryt
Malgorzata
M
Czernin
Johannes
J
Phelps
Michael E
ME
Silverman
Daniel H S
DH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011379:Prognosis; D011877:Radionuclide Imaging; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D005462:Fluorine Radioisotopes; D017239:Paclitaxel