Biodistribution and predictive value of 18F-fluorocyclophosphamide in mice bearing human breast cancer xenografts.

Abstract

UNLABELLED:

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.

CONCLUSION:

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.

• Authors: Amanda L Kesner, Wei-Ann Hsueh, Nwe Linn Htet, Betty S Pio, Johannes Czernin, Mark D Pegram, Michael E Phelps, Daniel H S Silverman
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 48 Issue 12 Pg. 2021-7 (Dec 2007) ISSN: 0161-5505 [Print] United States
• PMID: 18006620 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorine Radioisotopes
• Radiopharmaceuticals
• Cyclophosphamide

Topics

• Animals
• Cell Line, Tumor
• Cyclophosphamide (pharmacokinetics, therapeutic use)
• Female
• Fluorine Radioisotopes
• Humans
• Mammary Neoplasms, Experimental (drug therapy, metabolism, radionuclide imaging)
• Mice
• Positron-Emission Tomography
• Predictive Value of Tests
• Radiopharmaceuticals
• Tissue Distribution