noninvasive nuclear medicine test to determine sensitivity to cyclophosphamide
and perhaps will be developed further to predict sensitivity to other chemotherapies
Among the authors is Mark Pegram, her2 breast cancer specialist
J Nucl Med. 2007 Nov 15 [Epub ahead of print] Links
Biodistribution and Predictive Value of 18F-Fluorocyclophosphamide in Mice Bearing Human Breast Cancer Xenografts.
Kesner AL, Hsueh WA, Htet NL, Pio BS, Czernin J, Pegram MD, Phelps ME, Silverman DH.
Ahmanson Biological Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California.
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.
PMID: 18006620 [PubMed - as supplied by publisher]
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