Abstract:
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Purpose: To monitor vascularisation of subcutaneously grown human squamous
cell carcinomas in nude mice treated with a VEGF-receptor II antibody, using
dynamic magnetic resonance imaging (MRI).
Methods and Materials: 12 nude mice with subcutaneously grown HaCaT-ras RT3
tumors were studied. 6 mice were treated with 800 ug of a VEGF-receptor
antibody subutaneously injected every second day, 6 were used as controls. All
animals were examined before and 1, 2, 4, 7 and 14 days after starting
antiangiogenic treatment in a 1.5T whole body MR scanner, using a
self-developed animal coil and Gd-DTPA enhanced dynamic T1w sequences. Using a
two compartment model, the dynamic date was parameterized in amplitude
(relative increase on signal intensity) and kep (exchange rate constant). In a
separate setting with 10 nude mice, MR results were compared with vessel
staining (CD31) using immunofluorescence images.
Results: Two weeks after antibody treatment the mean volume of treated tumors
(83 mm3) was significantly lower (p=0.001) than of untreated ones (1208 mm3).
Treatment effect was also displayed in the MR amplitudes, which were decreased
in treated tumors as soon as 2 days post treatment as compared with untreated
tumors. The highest difference in amplitudes was observed 4 days post
treatment, when amplitudes of treated tumors were 61% lower (p=0.02). After one
week, amplitudes in treated tumors increased again and ultimately reached
higher values than in the control group. Microvessel density changed in line
with the amplitudes. kep remained unchanged in both groups.
Conclusion: Dynamic MRI is capable of detecting early effects of
anti-angiogenic therapy. A seemingly paradoxical, late increase of amplitudes
can be explained by a collapse of the gross tumor volume and a tighter grouping
of large vessels at the tumor border. Therefore, for interpreting dynamic data
of tumor vascularisation, alterations of tumor size have to be taken in
account. (Imclone provided the antibody DC101.)
Questions about this event email: F.Kiessling@dkfz.de
Kiessling MD, F,
Effect of Anti-VEGF Receptor II Antibody (DC101) on Vascularisation of Human Squamous Cell Carcinomas in Nude Mice Monitored by Dynamic Magnetic Resonance Imaging. Radiological Society of North America 2003 Scientific Assembly and Annual Meeting, November 30 - December 5, 2003 ,Chicago IL.
http://archive.rsna.org/2003/3104792.html
