We present an intensity-based non-rigid registration approach for normalizing 3D multi-channel microscopy images of cell nuclei. A main problem with cell nuclei images is that the intensity structure of different nuclei differs very much, thus an intensity-based registration scheme cannot be used directly. Instead, we first perform a segmentation of the images, smooth them by a Gaussian filter, and then apply an intensity-based algorithm. To improve the convergence rate of the algorithm, we propose an adaptive step length optimization scheme and also employ a multi-resolution scheme. Our approach has been successfully applied using 2D cell-like synthetic images, 3D phantom images as well as 3D multichannel microscopy images representing different chromosome territories and gene regions (BACs). We also describe an extension of our approach which is applied for the registration of 3D+t (4D) image series of moving cell nuclei.