ABSTRACT
Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), ultrasound and near-infrared spectrometry were used to evaluate tumor vessel integrity. Finally, tumors were explanted and VEGF, basic fibroblast growth factor (bFGF), vessel density, proliferation and apoptotic activity were analyzed by immunohistochemistry. Irradiation caused VEGF release and we found evidence for VEGF-mediated vessel protection. In the tumors derived from the combined treatment, blood volume was decreased, and apoptotic indices were increased. Remarkably, bFGF levels and proliferative indices were also increased. Combined irradiation/anti-VEGF treatment resulted in the desired VEGF depletion and increased tumor cell apoptosis. Nonetheless, bFGF and proliferation also increased, possibly suggesting a compensatory response. The application of additional targeted drugs may help develop more effective SCC treatments.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Fibroblast Growth Factor 2/metabolism , Animals , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Cell Line, Tumor , Hemodynamics , Humans , Mice , Mice, Nude , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism , Xenograft Model Antitumor AssaysABSTRACT
PURPOSE: To compare three different autocalibrated parallel acquisition techniques (PAT) for quantitative and semiquantitative myocardial perfusion imaging. MATERIALS AND METHODS: Seven healthy volunteers underwent myocardial first-pass perfusion imaging at rest using an SR-TrueFISP pulse sequence without PAT and while using GRAPPA, mSENSE, and TSENSE. signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), normalized upslopes (NUS), and myocardial blood flow (MBF) were calculated. Artifacts, image noise, and overall image quality were qualitatively assessed. Furthermore, the relation between signal intensity (SI) and contrast medium (CM) concentration was determined in phantoms. RESULTS: Using PAT the linear range of the SR-TrueFISP sequence was increased about 40%. All three PAT methods introduced significant loss in SNR and CNR. GRAPPA yielded slightly better values then mSENSE and TSENSE. Both SENSE techniques introduced significantly residual aliasing artifacts. Image noise was increased with all three PAT methods. However, overall image quality was reduced only with mSENSE. Even though GRAPPA yielded smaller NUS values than non-PAT, mSENSE, and TSENSE, no differences were found in MBF between all applied techniques. CONCLUSION: Quantitative and semiquantitative myocardial perfusion imaging can benefit from PAT due to shorter acquisition times and increased linearity of the pulse sequence. GRAPPA and TSENSE turned out to be well suited for quantitative myocardial perfusion imaging.
