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.
UNLABELLED: In mice bearing humanbreast 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 humanbreast 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: Helen Lee; Anthony F Shields; Barry A Siegel; Kathy D Miller; Ian Krop; Cynthia X Ma; Patricia M LoRusso; Pamela N Munster; Karen Campbell; Daniel F Gaddy; Shannon C Leonard; Elena Geretti; Stephanie J Blocker; Dmitri B Kirpotin; Victor Moyo; Thomas J Wickham; Bart S Hendriks Journal: Clin Cancer Res Date: 2017-03-15 Impact factor: 12.531
Authors: Adam L Kesner; Wei-Ann Hsueh; Johannes Czernin; Henry Padgett; Michael E Phelps; Daniel H S Silverman Journal: Mol Imaging Biol Date: 2008-08-05 Impact factor: 3.488
Authors: F Röhrig; S Vorlová; H Hoffmann; M Wartenberg; F E Escorcia; S Keller; M Tenspolde; I Weigand; S Gätzner; K Manova; O Penack; D A Scheinberg; A Rosenwald; S Ergün; Z Granot; E Henke Journal: Oncogene Date: 2016-06-06 Impact factor: 9.867