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Abstract #2274

Semi-Parametric Analysis of Gd-DTPA Kinetics in Glioblastoma

Ruedi E. Port1, Lu Xu1, Lisa J. Bernstein2, Timothy P. L. Roberts3, Daniel P. Barboriak4, Nicholas van Bruggen5

1Early Development PKPD, Genentech Inc., South San Francisco, CA, USA; 2Biostatistics, Genentech Inc., South San Francisco, CA, USA; 3Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; 4Radiology, Duke University Medical Center, Durham, NC, USA; 5Biomedical Imaging, Genentech Inc., South San Francisco, CA, USA

Gd-DTPA kinetics in tissue are often described by assuming an impulse-response function (IRF) comprised of a delta function and one exponential. Kinetics in malignant tumors typically require adding a second exponential. We propose to calculate non-compartmental descriptors of the IRF within the observation period: area under the curve (AUC) and mean residence time (MRT). AUC in malignant glioblastoma is consistently reduced 24 hours after dosing of bevacizumab while MRT remains apparently unchanged. -- The proposed analysis avoids model overinterpretation and prediction beyond the time of measuring, yet enables mechanistic hypotheses generating.