Internal dosimetry calculation of Cu-64 NOTA trastuzumab in human breast cancer xenograft mouse using Monte Carlo simulation.

Objectives Image based internal dosimetry studies have been performed to evaluate the characteristics of radiopharmaceuticals. Tumor position and object size must be considered in internal absorbed dose calculation. We performed calculations of internal dosimetry of organs and tumor in xenograft model of human breast cancer using individual mouse S-values of Monte Carlo simulation.

Methods Tumor was implanted subcutaneous with HER2 positive human breast cancer cells on the right flank of nude mouse. The tumor bearing mouse was injected with 7.4 MBq of Cu-64 NOTA trastuzumab in 100 ul volume intravenously. Small animal PET imaging of tumor bearing mouse was performed on a dedicated small animal PET/CT scanner (Inveon, Siemens Healthcare, Malvern, PA). Mouse images were acquired at 6 time points after the radiotracer administration (1, 2, 6, 24, 48, and 70 h). Subcutaneous tumor and organs were segmented by mean-based region growing 3D segmentation method and manually. Residence times were computed via time activity curves of the acquired region segmented PET time series data. The region segmented CT images with density information were used for calculations of absorbed fractions. S-values were calculated using Geant4 Monte Carlo simulations for calculation of Cu-64 absorbed dose. Internal dosimetry was evaluated by residence times of PET images and Monte Carlo-based S-value.

Results HER2 positive human breast cancer had significant uptake of Cu-64 NOTA trastuzumab. Segmented region based uptake for the liver, heart, and tumor were 6.82, 11.87, and 25.41 %ID/g, respectively. Representative residence time was 1.47 h for the liver, 2.64 h for the heart and 2.84 h for the tumor. Monte Carlo simulated S-value was 2.11E-02 for liver, 1.05E-01 for heart and 3.28E-01 mGy/MBq for the tumor. Calculated absorbed doses for the liver, heart, tumor, and total body were 2.11E-02, 2.77E-01, 9.30E-01, and 2.04E+00 mGy/MBq, respectively.

Conclusions We calculated the internal dosimetry of Cu-64 labeled trastuzumab in small animal PET images using Monte Carlo-based tumor and organs S-value. Our method will be applied for the treatment response assessment and internal dose calculation of convergence radiopharmaceutical.