(18)F-fluromisonidazole PET imaging as a biomarker for the response to 5,6-dimethylxanthenone-4-acetic acid in colorectal xenograft tumors Journal Article

   

Authors:	Oehler, C.; O'Donoghue, J. A.; Russell, J.; Zanzonico, P.; Lorenzen, S.; Ling, C. C.; Carlin, S.
Article Title:	(18)F-fluromisonidazole PET imaging as a biomarker for the response to 5,6-dimethylxanthenone-4-acetic acid in colorectal xenograft tumors
Abstract:	The aim of this study was to evaluate 18F-fluromisonidazole (18F-FMISO) PET for monitoring the tumor response to the antivascular compound 5,6-dimethylxanthenone-4-acetic acid (DMXAA; vadimezan). Methods: 18F-FMISO PET was performed 3 h before and 24 h after treatment with DMXAA (20 mg/kg) in mice bearing HT29 xenograft tumors. Pimonidazole was coadministered with the first 18F-FMISO injection, and 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5) was coadministered with the second one. Hoechst 33342 was administered 5 min before sacrifice. Digital autoradiograms of tumor sections were acquired; this acquisition was followed by immunofluorescence microscopic visualization of pimonidazole, EF5, the Hoechst 33342, CD31, and α-smooth muscle actin. Results: DMXAA treatment resulted in a marked reduction in the 18F-FMISO mean standardized uptake value (SUVmean) in approximately half of the treated tumors. The reduction in SUVmean correlated with a decrease in the fraction of tumor area staining positive for both EF5 and pimonidazole. Compared with untreated controls, tumors with decreasing SUVmean had significantly fewer perfused microvessels. Conclusion: 18F-FMISO PET could distinguish between different tumor responses to DMXAA treatment. However, a reduction in 18F-FMISO SUVmean after DMXAA treatment was indicative of reduced perfusion and therefore delivery of 18FFMISO, rather than a reduction in tumor hypoxia. Copyright © 2011 by the Society of Nuclear Medicine, Inc.
Keywords:	controlled study; treatment outcome; human cell; angiogenesis inhibitor; nonhuman; antineoplastic agents; positron emission tomography; methodology; antineoplastic agent; sensitivity and specificity; radiopharmaceuticals; reproducibility; reproducibility of results; mouse; animal; animals; mice; animal tissue; tumor volume; animal experiment; animal model; tumor xenograft; colorectal carcinoma; hypoxia; colorectal neoplasms; alpha smooth muscle actin; diagnostic agent; drug uptake; nude mouse; mice, nude; colorectal tumor; drug response; positron-emission tomography; radiopharmaceutical agent; drug derivative; scintiscanning; 1 fluoro 3 (2 nitro 1 imidazolyl) 2 propanol f 18; hoe 33342; pimonidazole; 1 fluoro 3 (2 nitro 1 imidazolyl) 2 propanol; misonidazole; angiogenesis inhibitors; tumor vascularization; pet; cell strain ht29; ht29 cells; autoradiography; immunofluorescence microscopy; cd31 antigen; 2 (2 nitro 1h imidazol 1 yl) n (2,2,3,3,3 pentafluoropropyl)acetamide; 18f-fmiso; antivascular treatment; dmxaa; vadimezan; 5,6 dimethylxanthenoneacetic acid; 5,6-dimethylxanthenoneacetic acid; xanthone derivative; xanthones
Journal Title:	Journal of Nuclear Medicine
Volume:	52
Issue:	3
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2011-03-01
Start Page:	437
End Page:	444
Language:	English
DOI:	10.2967/jnumed.110.081372
PUBMED:	21321262
PROVIDER:	scopus
PMCID:	PMC3394183
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79952796286&partnerID=40&md5=70ecf3ee9cb671ae90323b6c7cdf1e64
Notes:	--- - "Export Date: 23 June 2011" - "CODEN: JNMEA" - "Source: Scopus"

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