Image-based small-scale 3D-dosimetry in targeted alpha therapy using voxel dose-point kernels and alpha camera imaging of serial tissue sections

Objectives Targeted alpha therapy, TAT, is rapidly gaining increased clinical interest. The α-camera is an ex vivo high-resolution imager of alpha particles (J Nucl Med. 2010). Here we present a method for image-based small-scale 3D-dosimetry using voxel dose-point kernels (VDKs) and α-camera imaging.

Methods At-211-MX35-F(Ab’)2 was i.v.-injected in mice and intratumoral (OVCAR-3) activities was quantified by α-camera imaging of cryosections. Images were acquired for series of 13 consecutive 12 μm-thick tumor sections and then registered and stacked to a 3D-matrix of 12x12x12 μm voxels. VDKs were generated by an in-house Monte Carlo code. Using Matlab, the activity images were convoluted with the VDKs to calculate absorbed dose rate in each voxel. The center section (#7) in a series was used for further evaluation.

Results Non-uniform intra-tumoral activity distributions were found for time points up to >7 hours post injection, hpi. High activity areas (3-fold higher than the mean) corresponded to capillaries, stroma structures, and close-to-stroma tumor cells. As an example, the mean and maximum dose rates for a whole tumor section at 4 hpi was 0.12 and 1.09 mGy/s/MBq. The volume fractions for all voxels within the intervals 0-0.12, 0.12-0.2, 0.2-0.3 and 0.3-1.09 mGy/s/MBq were 0.57, 0.33, 0.08 and 0.02, respectively. The dose rate images and histograms (Suppl. data) showed large variations in intratumoral dose distribution. Absorbed dose for stroma-related cells were >2 times higher than the tumor mean.

Conclusions Large variations in intratumoral dose rate distributions were seen. Small-scale dosimetry is thus needed to predict biological effects of TAT. Our method can be used also for EUD and BED and will aid in further development of TAT, e.g. in choosing targeting strategy or vectors sizes.

Research Support Swedish Cancer Society, Jubileumsklinikens Cancer Fond, Swedish Radiation Safety Authority, P.Falks Foundation for Research on Prostate Cancer and Assar Gabrielssons Fond.