The Experts below are selected from a list of 24 Experts worldwide ranked by ideXlab platform
Einar K Rofstad - One of the best experts on this subject based on the ideXlab platform.
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preclinical evaluation of gd dtpa and Gadomelitol as contrast agents in dce mri of cervical carcinoma interstitial fluid pressure
BMC Cancer, 2012Co-Authors: Tord Hompland, Christine Ellingsen, Einar K RofstadAbstract:High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or Gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm3 and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. When Gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.
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assessment of tumor hypoxia and interstitial fluid pressure by Gadomelitol based dynamic contrast enhanced magnetic resonance imaging
Radiotherapy and Oncology, 2011Co-Authors: Kristine Gulliksrud, Tord Hompland, Kanthi Galappathi, Einar K RofstadAbstract:Abstract Background and purpose Extensive hypoxia and high interstitial fluid pressure (IFP) in the primary tumor may cause resistance to radiation treatment and promote metastatic spread. The potential of Gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the extent of hypoxia and the level of interstitial hypertension in tumors was investigated in this preclinical study. Materials and methods Twenty-three A-07 tumors were subjected to DCE-MRI and subsequent measurement of IFP and fraction of pimonidazole-positive hypoxic tissue (HF Pim ). Parametric tumor images of K trans , v e , and V b Tofts (Tofts model) and of K i and V b Patlak (Patlak model) were produced by pharmacokinetic analyses of the DCE-MRI series. Results There was no correlation between IFP and HF Pim in the tumors. K trans and K i decreased significantly with increasing HF Pim , whereas V b Tofts and V b Patlak increased significantly with increasing IFP. Conclusion Information on both the extent of hypoxia and the level of interstitial hypertension in A-07 tumors can be derived from a single DCE-MRI series by using Gadomelitol as contrast agent.
Tord Hompland - One of the best experts on this subject based on the ideXlab platform.
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preclinical evaluation of gd dtpa and Gadomelitol as contrast agents in dce mri of cervical carcinoma interstitial fluid pressure
BMC Cancer, 2012Co-Authors: Tord Hompland, Christine Ellingsen, Einar K RofstadAbstract:High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or Gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm3 and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. When Gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.
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assessment of tumor hypoxia and interstitial fluid pressure by Gadomelitol based dynamic contrast enhanced magnetic resonance imaging
Radiotherapy and Oncology, 2011Co-Authors: Kristine Gulliksrud, Tord Hompland, Kanthi Galappathi, Einar K RofstadAbstract:Abstract Background and purpose Extensive hypoxia and high interstitial fluid pressure (IFP) in the primary tumor may cause resistance to radiation treatment and promote metastatic spread. The potential of Gadomelitol-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the extent of hypoxia and the level of interstitial hypertension in tumors was investigated in this preclinical study. Materials and methods Twenty-three A-07 tumors were subjected to DCE-MRI and subsequent measurement of IFP and fraction of pimonidazole-positive hypoxic tissue (HF Pim ). Parametric tumor images of K trans , v e , and V b Tofts (Tofts model) and of K i and V b Patlak (Patlak model) were produced by pharmacokinetic analyses of the DCE-MRI series. Results There was no correlation between IFP and HF Pim in the tumors. K trans and K i decreased significantly with increasing HF Pim , whereas V b Tofts and V b Patlak increased significantly with increasing IFP. Conclusion Information on both the extent of hypoxia and the level of interstitial hypertension in A-07 tumors can be derived from a single DCE-MRI series by using Gadomelitol as contrast agent.
Christine Ellingsen - One of the best experts on this subject based on the ideXlab platform.
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preclinical evaluation of gd dtpa and Gadomelitol as contrast agents in dce mri of cervical carcinoma interstitial fluid pressure
BMC Cancer, 2012Co-Authors: Tord Hompland, Christine Ellingsen, Einar K RofstadAbstract:High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or Gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm3 and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. When Gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.
Robert N Muller - One of the best experts on this subject based on the ideXlab platform.
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in vitro relaxometric and luminescence characterization of p792 Gadomelitol vistarem an efficient and rapid clearance blood pool mri contrast agent
European Journal of Inorganic Chemistry, 2005Co-Authors: Luce Vander Elst, Isabelle Raynal, Marc Port, Pierre Tisnes, Robert N MullerAbstract:P792 (Gadomelitol, Vistarem®), a hydrophilic high molecular weight (MW = 6473 g/mol) derivative of DOTA-Gd is a rapid clearance blood pool agent (RCBPA) characterized by high proton relaxivities r1 and r2 at 310 K in the current range of clinical imaging magnetic fields. Luminescence data of the EuIII complex, as expected for this type of DOTA derivative, agree with the presence of one water molecule in the first coordination sphere of the lanthanide ion. The stability of the water proton longitudinal relaxation rate in the presence of zinc(II) and phosphate ions showed that the transmetallation by ZnII ions is negligible. The temperature dependence of the water oxygen-17 transverse relaxation rate gave a τM smaller than 100 ns at 310 K. No significant increase of longitudinal or transverse relaxation rates in serum or HSA solution was noticed, precluding association with high molecular weight blood components. The proton Nuclear Magnetic Relaxation Dispersion (NMRD) profile of the water solution showed a maximum of longitudinal relaxivity between 20 and 40 MHz (r1 ≈ 40 s–1 mM–1 at 310 K). Fitting of the proton NMRD curve by the classical outersphere and innersphere models, including or not additional second sphere water molecules, gave a rotational correlation time of approximately 2 to 3 ns and a large value of the electronic relaxation time at low field (τSO ≈ 500 ps). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Stephen R Wedge - One of the best experts on this subject based on the ideXlab platform.
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effects of azd2171 and vandetanib zd6474 zactima on haemodynamic variables in an sw620 human colon tumour model an investigation using dynamic contrast enhanced mri and the rapid clearance blood pool contrast agent p792 Gadomelitol
NMR in Biomedicine, 2008Co-Authors: Daniel P Bradley, J L Tessier, D Checkley, Hideto Kuribayashi, John C Waterton, Jane Kendrew, Stephen R WedgeAbstract:The effect of two novel therapeutic agents on tumour haemodynamics was investigated using a fast dynamic contrast-enhanced (DCE)-MRI protocol (0.5 s/image) sensitive to signal changes in both the vascular input function and tumour during the administration of the macromolecular rapid clearance blood pool agent (MM-RCBPA), Gadomelitol (P792, Vistarem). This enabled simultaneous measurement of the tumour blood flow per unit volume of tissue (F/V(T), mL/s/mL), the fractional plasma volume (V(p), %), and the permeability surface area product per unit volume of tissue (PSrho, s(-1)) in subcutaneous SW620 human colorectal tumour xenografts grown in nude rats before and after (at 0 and 22 h; imaging at 24 h) acute treatment with AZD2171 (3 mg/kg) and vandetanib (ZD6474, Zactima; 50 mg/kg), which have inhibitory activity against vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase. MRI was performed at 4.7 T using a single-slice, modified, T(1)-weighted, spoiled gradient-echo technique. Both compounds reduced Gadomelitol uptake into the tumour. AZD2171 and vandetanib, respectively, (a) greatly reduced PSrho to 19.7 +/- 9.5% and 28.9 +/- 14.1% of baseline (P = 0.007 and P = 0.02), (b) markedly reduced V(p) to 31.2 +/- 19.1% and 54.8 +/- 21.2% of baseline (P = 0.015 and P = 0.09), and (c) had no significant effect on F/V(T). There was no significant difference between groups treated with AZD2171 and vandetanib when each variable was compared. The reductions in PSrho and V(p) are consistent with inhibition of VEGF signalling. AZD2171 (3 mg/kg) and vandetanib (50 mg/kg) were also found to produce a comparable chronic inhibition of SW620 tumour growth (89% for both). This study shows that DCE-MRI using an MM-RCPBA can be used to distinguish tumour vascular flow, volume, and permeability surface area product in a tumour model, and enables the acute effects of VEGF signalling inhibition to be examined in detail.
