166Ho-microsphere liver radiotherapy: a preclinical SPECT dosimetry study in the pig

Liver metastases cause the majority of deaths from colorectal cancer and response to chemotherapy is poor. Intrahepatic arterial 90Y-microspheres may induce tumour regression but the beta-radiation dose is variable and cannot be determined in patients. The 81 keV gamma emission of holmium-166 (166Ho) was used to determine, by single photon emission computed tomographic (SPECT) imaging, the beta-radiation absorbed dose to normal liver in pigs following intrahepatic arterial administration of 166Ho-microspheres. The SPECT system was calibrated with anthropomorphic liver phantoms containing known activity concentrations of 166Ho-chloride. The relationship of SPECT counts to phantom activity concentration was linear with a correlation coefficient of r = 0.996. The SPECT pattern of liver distribution following successive administrations of tracer activities of 166Ho-microspheres was similar. The ratio of initial to total SPECT estimates of mean activity concentration in regions of interest, from which anatomically matched biopsy samples were later obtained and counted in an ionization chamber, showed good correlation (r = 0.924). Prospective SPECT dosimetry performed on a tracer activity of 166Ho-microspheres predicted the total administered activity required to deliver a prescribed radiation absorbed dose of 25 Gy to the liver within an error of +/- 8%. This study demonstrates the feasibility of prospective control of the absorbed radiation dose to the critical normal organ by SPECT dosimetry on a tracer dose of 166Ho-microspheres prior to administration of a therapy dose.