In Vivo Monitoring of Angiogenesis Inhibitory Treatment Effects by Dynamic Contrast-Enhanced Computed Tomography in a Xenograft Tumor Model
| Autor: | Robert C. Brasch, Benjamin M. Yeh, Hans-Juergen Raatschen, Yanjun Fu, David M. Shames, Hubertus Pietsch |
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| Rok vydání: | 2009 |
| Předmět: |
Vascular Endothelial Growth Factor A
Dendrimers Pathology medicine.medical_specialty Bevacizumab Angiogenesis Iohexol Angiogenesis Inhibitors Breast Neoplasms Antibodies Monoclonal Humanized Sensitivity and Specificity Article Polyethylene Glycols Rats Nude In vivo PEG ratio Animals Medicine Radiology Nuclear Medicine and imaging Microvessel business.industry Antibodies Monoclonal Reproducibility of Results General Medicine Rats Angiogenesis inhibitor Radiographic Image Enhancement Monoclonal Feasibility Studies Female Tomography X-Ray Computed business Nuclear medicine medicine.drug |
| Zdroj: | Investigative Radiology. 44:265-270 |
| ISSN: | 0020-9996 |
| Popis: | Rationale and Objectives: To evaluate the potential of dynamic CT enhanced by iohexol or a novel macromolecular contrast agent, PEG 12ooo -Gen4-triiodo, to monitor microvascular changes in tumors treated with the angiogenesis inhibitor bevacizumab. Materials and Methods: Ten female nude rats with MDA-MB 435 xenograft tumors were treated with 1 mg intraperitoneal bevacizumab when tumors reached 1 cm diameter and, for 4 rats, treated again 7 days later. Just before and 24 hours after the first injection of anti-VEGF antibody, the tumors were imaged by dynamic CT scans enhanced with PEG 12000 -Gen4-triiodo (n = 3 rats) or iohexol (n = 3 rats). The other 4 rats underwent dynamic CT scans enhanced with PEG 12000 -Gen4-triiodo just before and 24 hours after the second injection of anti-VEGF antibody. Microvascular leakiness (K PS ) was calculated for the tumors using a 2-compartment tissue model. Results: PEG 12000 -Gen4-triiodo-enhanced CT scans showed progressive reductions in K PS from day 1 to 2 to 9 (from 2.55 to 1.27 to 0.69 μL min -1 cm -3 , respectively, P < 0.005 for each comparison of day 1-2 and day 2-9). No significant difference was seen in the K PS estimates derived from iohexol-enhanced CT scans obtained before or after treatment (276 vs. 223.8 μL min -1 cm -3 , respectively, P = 0.54). The microvascular leak (K PS ) was significantly larger for iohexol than for PEGi2ooo-Gen4-triiodo-enhanced CT, P < 0.05. Conclusion: Dynamic macromolecular contrast-enhanced CT can be used to monitor serial decreases in tumor microvessel leakiness induced by repeated doses of an angiogenesis inhibitor drug. |
| Databáze: | OpenAIRE |
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