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Parametric Images of Antibody Pharmacokinetics Based on Serial Quantitative Whole-Body Imaging and Blood Sampling

¹ Department of Medical Radiation Physics, Clinical Sciences, Lund University Hospital, Lund, Sweden; ² Department of Oncology, Clinical Sciences, Lund University Hospital, Lund, Sweden; and ³ Departments of Psychiatry and Radiology, New York State Psychiatric Institute, Columbia University, New York, New York

Correspondence: For correspondence or reprints contact: Katarina Sjögreen Gleisner, PhD, Department of Medical Radiation Physics, Barngatan 2:1, Lund University Hospital, S-22185 Lund, Sweden. E-mail: katarina.sjogreen{at}med.lu.se

We present a method for pharmacokinetic modeling of distributions of ¹¹¹In-labeled monoclonal antibodies (mAbs) on individual pixels of planar scintillation-camera images. Methods: The method is applied to 2 sets of clinical whole-body images, each consisting of 6 consecutive images acquired over a week. Quantification is performed on a pixel basis, yielding images in units of Bq/pixel. The images acquired on the different occasions are registered using a nonrigid method, and for each pixel location a time–activity curve is obtained for which kinetic modeling is performed. The ¹¹¹In-mAb is assumed to be located in either the vascular or the extravascular space. The vascular content is assumed to follow the global blood kinetics as determined from blood samples, together with a model parameter that describes the fraction of the whole-body blood volume present in the particular pixel. The rate of change of the extravascular compartment is described by a linear 1-tissue-compartment model with 2 rate constants, K'₁ and k₂, reflecting extravasation and washout, respectively. The model is optimized for each pixel position with regard to the values of the 3 parameters (, K'₁, and k₂), resulting in 3 parametric images. From these, images of the cumulated activity in vascular and extravascular spaces are calculated, as is an image of the rate-constants ratio, which is closely related to the volume of distribution. Results: The resulting parametric images are analyzed in terms of the appearance of the time–activity curves at various locations. Results also include interpretation of the parametric images in their clinical context, and the location of regions that exhibit high extravasation and a low washout rate is compared with confirmed malignant sites. Conclusion: Parametric imaging allows the study and analysis of the spatial and temporal distributions of mAbs simultaneously. Parametric imaging enhances regions where the pharmacokinetics differ from the surrounding tissue and provides a tool to detect and locate unexpected kinetic behavior, which is sometimes characteristic of malignant tissue. For dosimetry in radionuclide therapy, parametric imaging offers a less biased means of analyzing serial mAb images than traditional region-of-interest–based analysis.

Key Words: parametric image • pharmacokinetic modeling • radioimmunoimaging • monoclonal antibody • rituximab

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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