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.