ABSTRACT
BACKGROUND: EndoTAG-1 (ET), a novel formulation of cationic liposomes carrying embedded paclitaxel (Taxol), shows antitumoral activity, targeting tumor endothelial cells in solid tumors. Patients with advanced metastatic cancer were evaluated investigating effects on pharmacokinetics and tumor vasculature using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and contrast-enhanced ultrasound (CEUS). PATIENTS AND METHODS: The pharmacokinetic (PK) profile of ET (22 mg/m(2) i.v.) was evaluated after single and repeated doses. DCE-MRI and CEUS explored hepatic metastases before, during and after the 4-week treatment cycle. Angiogenic biomarkers were assessed. Tumor response was evaluated by modified RECIST. RESULTS: The PK profile demonstrated slight accumulation of paclitaxel after repeated doses. DCE-MRI parameters K(trans) and/or iAUC(60) showed a trend to decrease. Changes of blood flow-dependent parameters of DCE-MRI and CEUS were well correlated. Angiogenic biomarkers revealed no clear trend. ET was generally well tolerated; common toxic effects were fatigue and hypersensitivity reactions. Nine (9 of 18) patients had stable disease after the first treatment cycle. Four patients without disease progression continued treatment. CONCLUSIONS: This study including multiple pretreated patients with different metastatic cancer revealed individually distinctive hemodynamic alterations by DCE-MRI. The PK profiles of ET were similar as observed previously.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Breast Neoplasms/pathology , Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Paclitaxel/therapeutic use , Pancreatic Neoplasms/pathology , Adult , Aged , Angiogenesis Inhibitors/pharmacokinetics , Angiogenesis Inhibitors/pharmacology , Angiotensin II/blood , Area Under Curve , Breast Neoplasms/blood , Breast Neoplasms/drug therapy , Colorectal Neoplasms/blood supply , Colorectal Neoplasms/drug therapy , Contrast Media , Endothelin-1/blood , Female , Humans , Interleukins/blood , Liposomes , Liver Neoplasms/blood supply , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Magnetic Resonance Imaging/methods , Male , Middle Aged , Paclitaxel/pharmacokinetics , Paclitaxel/pharmacology , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/drug therapy , Ultrasonography , Vascular Endothelial Growth Factor A/bloodSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Indoles/therapeutic use , Liver Neoplasms/secondary , Pyrroles/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor/analysis , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Colorectal Neoplasms/pathology , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Indoles/administration & dosage , Indoles/pharmacokinetics , Leucovorin/adverse effects , Leucovorin/therapeutic use , Magnetic Resonance Imaging , Pyrroles/administration & dosage , Pyrroles/pharmacokinetics , SunitinibABSTRACT
BACKGROUND: In oxygen-enhanced lung MRI, difference maps of acquisitions during inhalation of room air and pure oxygen are calculated to assess lung function. The purpose of this study was to analyze how the calculation of these difference maps depends on the delayed signal change after switching the gas supply. METHODS: Ten healthy volunteers were examined with an ECG and respiratory-triggered T1-weighting inversion recovery HASTE sequence with parallel imaging. Four blocks with 20 repetitions of up to 6 coronal slices were continuously acquired; in blocks 1 and 3 room air was supplied, in blocks 2 and 4 oxygen. Data were postprocessed, discarding between 0 and 19 repetitions after each change of gas supply before calculating the relative signal difference. RESULTS: The averaged relative signal difference increases from 9.4 to 17.4% when the number of discarded acquisitions increases; the ratio of signal difference and spatial standard deviation reaches a maximum at 5-8 discarded acquisitions. CONCLUSIONS: An optimized ratio of signal difference and statistical error is found if about 5-8 of 20 respiratory-triggered repetitions are discarded after each change of gas supply for the calculation of difference maps.
