Abstract | PURPOSE: To assess tumor fractional blood volume (xi), determined in vivo by susceptibility contrast magnetic resonance imaging (MRI) as a noninvasive imaging biomarker of tumor response to the vascular disrupting agent ZD6126. METHODS AND MATERIALS: The transverse MRI relaxation rate R(2)( *) of rat GH3 prolactinomas was quantified prior to and following injection of 2.5 mgFe/kg feruglose, an ultrasmall superparamagnetic iron oxide intravascular contrast agent, and xi (%) was determined from the change in R(2)( *). The rats were then treated with either saline or 50 mg/kg ZD6126, and xi measured again 24 hours later. Following posttreatment MRI, Hoechst 33342 (15 mg/kg) was administered to the rats and histological correlates from composite images of tumor perfusion and necrosis sought. RESULTS: Irrespective of treatment, tumor volume significantly increased over 24 hours. Saline-treated tumors showed no statistically significant change in xi, whereas a significant (p = 0.002) 70% reduction in xi of the ZD6126-treated cohort was determined. Hoechst 33342 uptake was associated with viable tumor tissue and was significantly (p = 0.004) reduced and restricted to the rim of the ZD6126-treated tumors. A significant positive correlation between posttreatment xi and Hoechst 33342 uptake was obtained (r = 0.83, p = 0.002), providing validation of the MRI-derived measurements of fractional tumor blood volume. CONCLUSIONS:
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Authors | Simon P Robinson, Franklyn A Howe, John R Griffiths, Anderson J Ryan, John C Waterton |
Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 69
Issue 3
Pg. 872-9
(Nov 01 2007)
ISSN: 0360-3016 [Print] United States |
PMID | 17889267
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzimidazoles
- Contrast Media
- Dextrans
- Fluorescent Dyes
- Magnetite Nanoparticles
- N-acetylcochinol-O-phosphate
- Organophosphorus Compounds
- Oxides
- ferumoxtran-10
- Iron
- bisbenzimide ethoxide trihydrochloride
- Ferrosoferric Oxide
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Topics |
- Animals
- Benzimidazoles
(pharmacokinetics)
- Blood Volume
(drug effects, physiology)
- Contrast Media
- Dextrans
- Female
- Ferrosoferric Oxide
- Fluorescent Dyes
(pharmacokinetics)
- Iron
- Magnetic Resonance Imaging
(methods)
- Magnetite Nanoparticles
- Organophosphorus Compounds
(therapeutic use)
- Oxides
- Pituitary Neoplasms
- Prolactinoma
(drug therapy, metabolism, physiopathology)
- Rats
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