No abstract available.
Antigens, CD34/metabolism ; Carcinoma, Hepatocellular/pathology/*radiography ; Contrast Media/chemistry/diagnostic use ; Gadolinium DTPA/chemistry/*diagnostic use ; Humans ; Immunohistochemistry ; Liver Neoplasms/pathology/*radiography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVE: To visualize tumor angiogenesis using the MRI contrast agent, Gd-DTPA-anti-VEGF receptor 2 antibody conjugate, with a 4.7-Tesla MRI instrument in a mouse model. MATERIALS AND METHODS: We designed a tumor angiogenesis-targeting T1 contrast agent that was prepared by the bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and an anti-vascular endothelial growth factor receptor-2 (VEGFR2) antibody. The specific binding of the agent complex to cells that express VEGFR2 was examined in cultured murine endothelial cells (MS-1 cells) with a 4.7-Tesla magnetic resonance imaging scanner. Angiogenesis-specific T1 enhancement was imaged with the Gd-DTPA-anti-VEGFR2 antibody conjugate using a CT-26 adenocarcinoma tumor model in eight mice. As a control, the use of the Gd-DTPA-anti-rat immunoglobulin G (Gd-DTPA-anti-rat IgG) was imaged with a tumor model in eight mice. Statistical significance was assessed using the Mann-Whitney test. Tumor tissue was examined by immunohistochemical analysis. RESULTS: The Gd-DTPA-anti-VEGFR2 antibody conjugate showed predominant binding to cultured endothelial cells that expressed a high level of VEGFR2. Signal enhancement was approximately three-fold for in vivo T1-weighted MR imaging with the use of the Gd-DTPA-anti-VEGFR2 antibody conjugate as compared with the Gd-DTPA-rat IgG in the mouse tumor model (p < 0.05). VEGFR2 expression in CT-26 tumor vessels was demonstrated using immunohistochemical staining. CONCLUSION: MR imaging using the Gd-DTPA-anti-VEGFR2 antibody conjugate as a contrast agent is useful in visualizing noninvasively tumor angiogenesis in a murine tumor model.
Adenocarcinoma/*pathology ; Animals ; Colonic Neoplasms/*pathology ; Contrast Media/chemistry/*diagnostic use ; Gadolinium DTPA/chemistry/*diagnostic use ; Immunoenzyme Techniques ; Magnetic Resonance Imaging/*methods ; Mice ; Mice, Nude ; Neovascularization, Pathologic/*diagnosis ; Rats ; Statistics, Nonparametric ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor Receptor-2/*antagonists & inhibitors/chemistry

The authors investigated objective response rate to high dose methotrexate (HDMTX)-based combination chemotherapy in primary central nervous system lymphoma (PCNSL), and sought to identify factors that influence response to HDMTX-based combination therapy. Prospective observational analysis was performed on 52 PCNSL patients. All patients received HDMTX (3.5 g/m2) and vincristine (1.4 mg/m2/day) for one day during weeks 1, 3, 5, 7, and 9, and procarbazine (100 mg/m2/day) for one week during weeks 1, 5, and 9. Forty-one patients (78.8%) achieved complete or partial remission. Higher objective response rates were observed for patients with: 1) age < 60 yr; 2) Eastern Cooperative Oncology Group (ECOG) performance score of < 2; 3) low risk status as defined by the International Extranodal Lymphoma Study Group; 4) p53 positivity; 5) XBP-1 negativity; 6) MUM-1 negativity; and 7) homogenous gadolinium enhancement in MR images. Multivariate analysis showed that ECOG performance score of < 2, low risk, negativity for XBP-1, homogenous gadolinium enhancement by MRI, and response to chemotherapy were associated with longer overall survival. In particular, it is interesting to note that patients with a PCNSL that is homogenously enhanced by gadolinium have a higher objective response rate, and a longer progression-free survival and overall survival.
Adult ; Age Factors ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Central Nervous System Neoplasms/*drug therapy/mortality ; Contrast Media/chemistry/diagnostic use ; DNA-Binding Proteins/metabolism ; Disease-Free Survival ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Gadolinium/chemistry/diagnostic use ; Humans ; Interferon Regulatory Factors/metabolism ; Lymphoma/*drug therapy/mortality ; Magnetic Resonance Imaging ; Male ; Methotrexate/*administration & dosage ; Middle Aged ; Odds Ratio ; Procarbazine/*administration & dosage ; Prospective Studies ; Recurrence ; Severity of Illness Index ; Transcription Factors/metabolism ; Tumor Suppressor Protein p53/metabolism ; Vincristine/*administration & dosage