Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media

Pradel, Clément; Siauve, Nathalie; Bruneteau, Gaëlle; Clémеnt, Olivier; Bazelaire, Cédric de; Frouin, F.; Wedge, Stephen R.; Tessier, Jean; Robert, Philippe; Frija, G.; Cuenod, Charles‐André

doi:10.1016/s0730-725x(03)00186-3

Cited by 68 publications

(66 citation statements)

References 25 publications

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“…First, RECIST has been shown to be poorly reproducible (21) and only mildly sensitive, as diameter measurement does not accurately reflect tumor volume (22). Moreover, in patients treated with antiangiogenic agents, the external residual volume found on anatomic imaging may not reflect the true residual tumor cell volume, and conventional imaging may underestimate therapeutic response in cases of stable disease (23,24).…”

Section: Discussionmentioning

confidence: 99%

Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An ¹⁸F-Fluoromisonidazole PET/CT Study

Hugonnet

Fournier²,

Médioni³

et al. 2011

J Nucl Med

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The aims of this cohort study were to evaluate initial tumor hypoxia in metastatic renal cell carcinoma (mRCC) and its changes after sunitinib treatment, using 18 F-fluoromisonidazole PET/CT, and investigate the possible prognostic value of initial tumor hypoxia or its changes under sunitinib therapy. Methods: Antiangiogenic-naive patients with mRCC were prospectively enrolled in this cohort study. Before initiation of sunitinib, CT defined up to 10 targets that were assessed at 1 and 6 mo according to the response evaluation criteria in solid tumors (RECIST). Pretreatment target uptake of 18 F-fluoromisonidazole was compared with uptake at 1 mo. Targets were considered hypoxic when their maximal standard uptake value was above mean blood value 1 2 SDs. Hypoxic volumes were also computed. Relationships between initial hypoxia status, initial degree of hypoxia, its change at 1 mo, and overall or progression-free survival (OS and PFS, respectively) were assessed by survival analysis. Results: Fifty-three patients were included. Median follow-up was 16.8 mo. 18 F-fluoromisonidazole uptake significantly decreased in initially hypoxic target metastases but did not change in others (222%, P , 10 24 , vs. 11.5%, P 5 0.77; P 5 10 23 between groups). Seventy-five percent of patients with hypoxic metastases were free of progressive disease at 4.8 mo (95% confidence interval, 2.99-11.83), compared with 11.3 mo (95% confidence interval, 3.08-36.9) for other patients (P 5 0.02), whereas OS was not significantly different. Changes in tumor hypoxia were not related to PFS or OS. Conclusion: Sunitinib reduced hypoxia in initially hypoxic RECIST target metastases but did not induce significant hypoxia in nonhypoxic RECIST target metastases. Patients with initially hypoxic targets have shorter PFS than others.

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Section: Discussionmentioning

confidence: 99%

Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An ¹⁸F-Fluoromisonidazole PET/CT Study

Hugonnet

Fournier²,

Médioni³

et al. 2011

J Nucl Med

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“…Turetschek et al found no relation between transendothelial permeability estimated with P792 and histologic parameters (microvessel density and tumor grade) in a breast cancer model (32). In a prostate cancer model, however, P792-based DCE-MRI was successfully used to monitor changes in permeability after anti-VEGF therapy (15). It is likely, therefore, that successful estimation of neovascular permeability with P792 is highly dependent not only on imaging and image processing methodology, but also on tumor type and grade.…”

Section: Discussionmentioning

confidence: 99%

“…Apparent hydrodynamic volume of P792 is 125 times greater than that of Gd-DOTA (gadoterate meglumine, Dotarem); as a result of this high molecular volume, P792 is characterized by a limited diffusion across normal endothelium and is therefore ideally suited to study hyperpermeable neoplastic vessels (14). Experimentally, P792 has been used to study permeability effects of antiangiogenesis therapy in a prostate cancer model (15).…”

Section: Mr Contrast Mediummentioning

confidence: 99%

Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

Ceelen

Smeets

Backes

et al. 2006

International Journal of Radiation Oncology*Biology*Physics

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“…A model with the same mathematical structure has been used previously for the evaluation of animal tumor models (39,40). Solving the equations produces the following formulae for R P and R E (the equivalent of Eqs.…”

Section: Tracer-kinetic Modeling Of Bbb-leakagementioning

confidence: 99%

Quantification of cerebral blood flow, cerebral blood volume, and blood–brain‐barrier leakage with DCE‐MRI

Sourbron

Ingrisch

Siefert

et al. 2009

Magnetic Resonance in Med

236

251

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Dynamic susceptibility contrast MRI (DSC-MRI) is the current standard for the measurement of Cerebral Blood Flow (CBF) and Cerebral Blood Volume (CBV), but it is not suitable for the measurement of Extraction Flow (EF) and may not allow for absolute quantification. The objective of this study was to develop and evaluate a methodology to measure CBF, CBV, and EF from T1-weighted dynamic contrast-enhanced MRI (DCE-MRI). A twocompartment modeling approach was developed, which applies both to tissues with an intact and with a broken Blood-BrainBarrier (BBB). The approach was evaluated using measurements in normal grey matter (GM) and white matter (WM) and in tumors of 15 patients. Accuracy and precision were estimated with simulations of normal brain tissue. All tumor and normal tissue curves were accurately fitted by the model. CBF (mL/100 mL/min) was 82 ± 21 in GM and 23 ± 14 in WM, CBV (mL/100 mL) was 2.6 ± 0.8 in GM and 1.3 ± 0.4 in WM. EF (mL/100 mL/min) was close to zero in GM (−0.009 ± 0.05) and WM (−0.03 ± 0.08). Simulations show an overlap between CBF values of WM and GM, which is eliminated when Contrast-to-Noise (CNR) is improved. The model provides a consistent description of tracer kinetics in all brain tissues, and an accurate assessment of perfusion and permeability in reference tissues. The measurement sequence requires optimization to improve CNR and the precision in the perfusion parameters. With this approach, DCE-MRI presents a promising alternative to DSC-MRI for quantitative bolustracking in the brain.

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Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media

Cited by 68 publications

References 25 publications

Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An ¹⁸F-Fluoromisonidazole PET/CT Study

Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An ¹⁸F-Fluoromisonidazole PET/CT Study

Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

Quantification of cerebral blood flow, cerebral blood volume, and blood–brain‐barrier leakage with DCE‐MRI

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Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media

Cited by 68 publications

References 25 publications

Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An 18F-Fluoromisonidazole PET/CT Study

Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An 18F-Fluoromisonidazole PET/CT Study

Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

Quantification of cerebral blood flow, cerebral blood volume, and blood–brain‐barrier leakage with DCE‐MRI

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Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An ¹⁸F-Fluoromisonidazole PET/CT Study

Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An ¹⁸F-Fluoromisonidazole PET/CT Study