Estimation of paclitaxel biodistribution and uptake in human-derived xenografts in vivo with (18)F-fluoropaclitaxel.
Paclitaxel (PAC) is widely used as a chemotherapy drug in the treatment of various malignancies, including breast, ovarian, and lung cancers. We examined the biodistribution of (18)F-fluoropaclitaxel ((18)F-FPAC) in mice with and without human breast cancer tumor xenografts by use of small-animal-dedicated PET (microPET) and clinically practical semiquantitative methods. We compared the PET data to data derived from direct harvesting and analysis of blood, organs, and breast carcinoma xenografts.


METHODS
PET data were acquired after tail vein injection of (18)F-FPAC in nude mice. Tracer biodistribution in reconstructed images was quantified by region-of-interest analysis. Biodistribution also was assessed by harvesting and analysis of dissected organs, tumors, and blood after coadministration of (18)F-FPAC and (3)H-PAC. (18)F content in each tissue was assessed with a gamma-well counter, and (3)H content was quantified by scintillation counting of solubilized tissue after (18)F radioactive decay.


RESULTS
The distributions of (18)F-FPAC and (3)H-PAC were very similar, with the highest concentrations in the small intestine, the lowest concentrations in the brain, and intermediate concentrations in tumor. Uptake in these and other tissues was not inhibited by the presence of more pharmacologic doses of unlabeled PAC. Administration of the P-glycoprotein modulator cyclosporine doubled the uptake of both (18)F-FPAC and (3)H-PAC into tumor.


CONCLUSIONS
PET studies with (18)F-FPAC can be used in conjunction with clinically practical quantification methods to yield estimates of PAC uptake in breast cancer tumors and normal organs noninvasively.
Gangloff
Anne
A
Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California.
Hsueh
Wei-Ann
WA
Kesner
Amanda L
AL
Kiesewetter
Dale O
DO
Pio
Betty S
BS
Pegram
Mark D
MD
Beryt
Malgorzata
M
Townsend
Allison
A
Czernin
Johannes
J
Phelps
Michael E
ME
Silverman
Daniel H S
DH
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D017239:Paclitaxel