The spatial biodistribution and dosimetry of holmium loaded microspheres after intratumoral injection.

Abstract

Intratumoral injections with radioactive holmium loaded microspheres (β Emax = 1.86 MeV, t1/2 = 26.8 h, γ-emission= 80 keV 6.7%) are used for the experimental treatment of untreatable solid tumors in veterinary patients. The results of this therapy are promising, but varying. Treatment outcome is believed to be optimal if the tumor is completely covered with a sufficient radiation dose. This implicates that treatment outcome depends on the dose distribution, and thus the spatial biodistribution of the microspheres inside the tumor. However, little is known about the distribution of the microspheres and their radiation dose after intratumoral injection. Therefore, a distribution study was conducted to elaborate the mechanism behind the spatial biodistribution. Furthermore, the use of different 3D imaging techniques were investigated for distribution evaluation, dosimetry and image guidance.

Experimentally induced Vx2 tumors in rabbits and spontaneous occurring solid tumors in veterinary patients were injected with suspended holmium microspheres. After injection, the tumors were removed and scanned by means of SPECT, CT, MRI and µCT. The microsphere distribution volume was compared for the different tumors. Holmium dosimetry for CT images was developed, using the increase in Houndsfield Units for increasing local holmium concentrations and 3D dose distribution kernels. Finally, some Vx2 tumors were injected under MRI guidance, to test the possibilities of image guided injections.

The number of injection sites turned out to be an inappropriate predictor of the microsphere distribution volume. The microspheres appear to follow the path of the least resistance after injection, which is dependent of multiple factors and varies per injection. After injection, quantification of the local holmium concentration and thus dosimetry is possible with all the mentioned 3D imaging techniques. SPECT imaging is only suitable for a rough estimation of the activity distribution in the body. MRI and CT can be used for more detailed tumor coverage estimations. CT turned out to be probably even more suitable for quantification in areas with a high holmium concentration, seen for example in veterinary patients, compared to MRI. Image guided holmium injections are possible with CT and MRI.

Because the microsphere distribution cannot be predicted based on the number of injection sites and greatly depends on intratumoral structure, more imaging during the treatment procedure is desirable. Combining this with the possibilities of dosimetry, it is possible to detect the untreated areas in the tumor. These insufficient treated areas can be retreated with subsequent holmium injections, which can be guided with MRI or CT. This will improve tumor coverage and therefore treatment outcome.