Assessment of antiangiogenic and antivascular therapeutics using MRI: recommendations for appropriate methodology for clinical trials

Leach, Martin O.; Brindle, Kevin M.; Evelhoch, Jeffrey L.; Griffiths, John R.; Horsman, Michael R.; Jackson, Alan; Jayson, Gordon C; Judson, Ian; Knopp, Michael V.; Maxwell, Ross J.; McIntyre, Dominick J.O.; Padhani, Anwar R.; Price, Patricia M; Rathbone, Richard; Rustin, G. J. S.; Tofts, PS; Tozer, Gillian M.; Vennart, W.; Waterton, John C.; Williams, S. R.; Workman, Paul

doi:10.1259/bjr/15917261

Cited by 128 publications

(94 citation statements)

References 8 publications

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“…The initial area under the time -concentration product curve (IAUC) for the first 150 s after administration of gadodiamide was then integrated, and the tumour data normalised to the median muscle IAUC to account for differences in the arterial input function between animals (Evelhoch, 1999). This methodology has been endorsed for use in studies of antivascular agents (Leach et al, 2003). The data were reviewed blind as images and normalised IAUC frequency histograms.…”

Section: Dynamic Contrast-enhanced Mrimentioning

confidence: 99%

Tumour dose response to the antivascular agent ZD6126 assessed by magnetic resonance imaging

et al. 2003

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ZD6126 is a vascular targeting agent that disrupts the tubulin cytoskeleton of proliferating neo-endothelial cells. This leads to the selective destruction and congestion of tumour blood vessels in experimental tumours, resulting in extensive haemorrhagic necrosis. In this study, the dose-dependent activity of ZD6126 in rat GH3 prolactinomas and murine RIF-1 fibrosarcomas was assessed using two magnetic resonance imaging (MRI) methods. Dynamic contrast-enhanced (DCE) MRI, quantified by an initial area under the time -concentration product curve (IAUC) method, gives values related to tumour perfusion and vascular permeability. Multigradient recalled echo MRI measures the transverse relaxation rate T Ã 2 , which is sensitive to tissue (deoxyhaemoglobin). Tumour IAUC and R Ã 2 (¼ 1=T Ã 2 ) decreased post-treatment with ZD6126 in a dose-dependent manner. In the rat model, lower doses of ZD6126 reduced the IAUC close to zero within restricted areas of the tumour, typically in the centre, while the highest dose reduced the IAUC to zero over the majority of the tumour. A decrease in both MRI end points was associated with the induction of massive central tumour necrosis measured histologically, which increased in a dose-dependent manner. Magnetic resonance imaging may be of value in evaluation of the acute clinical effects of ZD6126 in solid tumours. In particular, measurement of IAUC by DCE MRI should provide an unambiguous measure of biological activity of antivascular therapies for clinical trial.

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Section: Dynamic Contrast-enhanced Mrimentioning

confidence: 99%

Tumour dose response to the antivascular agent ZD6126 assessed by magnetic resonance imaging

et al. 2003

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“…Several articles (6,(16)(17)(18) have recommended careful consideration of methodological issues, including the acquisition of precontrast T 1 maps to facilitate calculation of the gadolinium concentration ([Gd]) as a function of time. Another important issue is the arterial input function (AIF).…”

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confidence: 99%

Dynamic contrast-enhanced MRI in ovarian cancer: Initial experience at 3 tesla in primary and metastatic disease

et al. 2010

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The aim of this study was to develop and demonstrate a methodology for dynamic contrast-enhanced MRI at 3 T in patients with advanced ovarian cancer and to report the results from pharmacokinetic modeling of the data. Nineteen patients with suspected advanced ovarian carcinoma (FIGO stage 3 or higher) were enrolled in this prospective study. Up to three marker lesions were identified: primary ovarian mass, omental ''cake'', and peritoneal deposits. Dynamic contrastenhanced MRI was performed using a three-dimensional T 1 -weighted gradient-echo acquisition with a temporal resolution of 1.6 sec, following intravenous administration of 0.1 mmol/ kg gadobutrol. Precontrast T 1 mapping, using an inversion-recovery fast gradient-echo sequence, was also performed. Imaging was completed in 18/19 patients, although two were subsequently excluded based on pathology results. Pharmacokinetic modeling of the data was performed according to the extended Kety model, using an arterial input function formed by concatenation of the Fritz-Hansen and Weinmann curves. No statistically significant differences were found between the results for the three marker lesions. In the future, this work will allow kinetic modeling results from ovarian dynamic contrast-enhanced MRI to be correlated with response to treatment. The high temporal resolution allows good characterization of the rapid contrast agent uptake in these vascular tumors.

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“…Tumor angiogenesis is a pathophysiologic process that has been linked to tumor viability and tumor grade (1,2). Therefore, antiangiogenic treatment strategies have proliferated during the past decade (3,4).…”

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Diagnostic accuracy and interobserver variability of pulsed arterial spin labeling for glioma grading

Kim

et al. 2008

Acta Radiol

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. Diagnostic accuracy and interobserver variability of pulsed arterial spin labeling for glioma grading. Acta Radiol 2008;49:450Á457.Background: Although pulsed arterial spin labeling (PASL) enables the reliable qualitative grading of brain tumors, its use in quantification for glioma grading may be hampered by the limited interobserver variability associated with low spatial resolution. Purpose: To assess the interobserver variability and diagnostic accuracy of the relative tumor perfusion signal intensity (rTPS) calculated using PASL in glioma grading. Material and Methods: Fifty-eight patients with 61 cerebral astrocytomas underwent conventional MR imaging and PASL. Receiver operating characteristic analyses were used to determine the optimum thresholds for tumor grading. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying highgrade gliomas were also calculated. Cohen's k statistic was used to determine the levels of interobserver variability in the quantitative analysis of PASL. Results: The sensitivity, specificity, PPV, and NPV for determining a high-grade glioma with conventional MR imaging were 77.1, 73.1, 79.4, and 70.4%, respectively. A threshold value of 1.28 for rTPS provided a sensitivity, specificity, PPV, and NPV of 82.9, 96.2, 96.7, and 80.6%, respectively. There was a statistically significant difference in the rTPS between low-and high-grade astrocytomas (1.14 vs. 1.47, P B0.05). In the interobserver variability analysis, substantial agreement was obtained for the quantitative rTPS measurement from PASL (k 00.72). Conclusion: Quantitative perfusion measurement with PASL can improve the diagnostic accuracy of preoperative glioma grading, as compared to the application of conventional imaging alone. However, the interobserver variability for quantification is substantial.

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Assessment of antiangiogenic and antivascular therapeutics using MRI: recommendations for appropriate methodology for clinical trials

Cited by 128 publications

References 8 publications

Tumour dose response to the antivascular agent ZD6126 assessed by magnetic resonance imaging

Tumour dose response to the antivascular agent ZD6126 assessed by magnetic resonance imaging

Dynamic contrast-enhanced MRI in ovarian cancer: Initial experience at 3 tesla in primary and metastatic disease

Diagnostic accuracy and interobserver variability of pulsed arterial spin labeling for glioma grading

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