title: 18F-FPPRGD2 and 18F-FDG PET of response to Abraxane therapy.
abstract: Abraxane (nanoparticle albumin-bound paclitaxel) is an anticancer drug approved by the Food and Drug Administration. However, the mechanism of action of Abraxane is complex, and no established biomarker is available to accurately monitor its treatment outcomes. The aim of this study was to investigate whether the integrin-specific PET tracer 18F-FPPRGD2 (investigational new drug 104150) can be used to monitor early response of tumors to Abraxane therapy.
  
  
  METHODS
  Orthotopic MDA-MB-435 breast cancer mice were treated with Abraxane (25 mg/kg every other day, 3 doses) or phosphate-buffered saline. Tumor volume was monitored by caliper measurement. PET scans were obtained before and at different times after the start of treatment (days 0, 3, 7, 14, and 21) using 18F-FPPRGD2 and 18F-FDG. The tumoricidal effect was also assessed ex vivo by immunohistochemistry.
  
  
  RESULTS
  Abraxane treatment inhibited the tumor growth, and a significant difference in tumor volume could be seen at day 5 after the initiation of treatment. The tumor uptake of 18F-FPPRGD2 in the Abraxane-treated group was significantly lower on days 3 and 7 than at baseline but returned to the baseline level at days 14 and 21, indicative of relapse of the tumors after the treatment was halted. Immunohistologic staining confirmed that the change of 18F-FPPRGD2 uptake correlated with the variation of integrin level in the tumor vasculature induced by Abraxane treatment. No significant change of tumor (rather than vascular) integrin expression was observed throughout the study. No significant decrease of 18F-FDG uptake was found between the treated and the control tumors on days 3, 14, and 21, although an increase in 18F-FDG tumor uptake of treated mice, as compared with the control mice, was found on day 7. The increase of 18F-FDG on day 7 was related to the inflammatory response during therapy.
  
  
  CONCLUSIONS
  Abraxane-mediated downregulation of integrin αvβ3 expression on tumor endothelial cells can be quantitatively visualized by PET. The change of integrin expression precedes that of tumor size. Consequently, 18F-FPPRGD2 PET is superior to 18F-FDG PET in monitoring early response to treatment, favoring its potential clinical translation.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892-2281, USA.
authors.forename: Xilin
authors.initials: X
authors.lastname: Sun
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Yan
authors.forename: Shuanglong
authors.initials: S
authors.lastname: Liu
authors.forename: Qizhen
authors.initials: Q
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
authors.forename: Baozhong
authors.initials: B
authors.lastname: Shen
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis* / Q000037:antagonists & inhibitors; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism*; D017239:Paclitaxel / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D023041:Xenograft Model Antitumor Assays
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; C574086:FPP(RGD)2; D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C047981:arginyl-glycyl-aspartic acid; D017239:Paclitaxel