Biodistribution and predictive value of 18F-fluorocyclophosphamide in mice bearing human breast cancer xenografts.
In mice bearing human breast cancer xenografts, we examined the biodistribution of (18)F-fluorocyclophosphamide ((18)F-F-CP) to evaluate its potential as a noninvasive prognostic tool for predicting the resistance of tumors to cyclophosphamide therapy.


METHODS
(18)F-F-CP was synthesized as we recently described, and PET data were acquired after administration of (18)F-F-CP in mice bearing human breast cancer xenografts (MCF-7 cells). Tracer biodistribution in reconstructed images was quantified by region-of-interest analysis. Distribution was also assessed by harvesting dissected organs, tumors, and blood, determining (18)F content in each tissue with a gamma-well counter. The mice were subsequently treated with cyclophosphamide, and tumor size was monitored for at least 3 wk after chemotherapy administration.


RESULTS
The distribution of harvested activity correlated strongly with distribution observed in PET images. Target organs were related to routes of metabolism and excretion. (18)F-F-CP uptake was highest in kidneys, lowest in brain, and intermediate in tumors, as determined by both image-based and tissue-based measurements. (18)F-F-CP uptake was not inhibited by coadministration of an approximately x700 concentration of unlabeled cyclophosphamide. PET measures of (18)F-F-CP uptake in tumor predicted the magnitude of the response to subsequent administration of cyclophosphamide.


CONCLUSIONS
Noninvasive assessment of (18)F-F-CP uptake using PET may potentially be helpful for predicting the response of breast tumors to cyclophosphamide before therapy begins.
Kesner
Amanda L
AL
Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California 90095-6942, USA.
Hsueh
Wei-Ann
WA
Htet
Nwe Linn
NL
Pio
Betty S
BS
Czernin
Johannes
J
Pegram
Mark D
MD
Phelps
Michael E
ME
Silverman
Daniel H S
DH
D000818:Animals; D045744:Cell Line, Tumor; D003520:Cyclophosphamide / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D003520:Cyclophosphamide