Abstract

The goal of this study was to suggest criteria for the determination of the optimal image reconstruction algorithm for image-based dosimetry of Cu-64 trastuzumab PET in a mouse model. Image qualities, such as recovery coefficient (RC), spill-over ratio (SOR), and non-uniformity (NU), were measured according to National Electrical Manufacturers Association (NEMA) NU4-2008. Mice bearing a subcutaneous tumor (, HER2 NCI N87) were injected with monoclonal antibodies (trastuzumab) with Cu-64. Preclinical mouse PET images were acquired at 4 time points after injection (2, 15, 40 and 64 h). Phantom and Cu-64 trastuzumab PET images were reconstructed using various reconstruction algorithms (filtered back projection (FBP), 3D reprojection algorithm (FBP-3DRP), 2D ordered subset expectation maximization (OSEM 2D), and OSEM 3D maximum a posteriori (OSEM3D-MAP)) and filters. The absorbed dose for the tumor and the effective dose for organs for Cu-64 trastuzumab PET were calculated using the OLINDA/EXM program with various reconstruction algorithms. Absorbed dose for the tumor ranged from 923 mGy/MBq to 1830 mGy/MBq with application of reconstruction algorithms and filters. When OSEM2D was used, the effective osteogenic dose increased from 0.0031 to 0.0245 with an increase in the iteration number (1 to 10). In the region of kidney, the effective dose increased from 0.1870 to 1.4100 when OSEM2D was used with iteration number 1 to 10. To determine the optimal reconstruction algorithms and filters, a correlation between RC and NU was plotted and selection criteria (0.9 < RC < 1.0 and < 10% of NU) were suggested. According to the selection criteria, OSEM2D (iteration 1) was chosen for the optimal reconstruction algorithm. OSEM2D (iteration 10) provided 154.7% overestimated effective dose and FBP with a Butterworth filter provided 20.9% underestimated effective dose. We suggested OSEM2D (iteration 1) for the calculation of the effective dose of Cu-64 trastuzumab on an Inveon PET scanner.

Highlights

  • Immuno-Positron Emission Tomographs (PETs) uses monoclonal antibodies that are labeled with positron-emitting radionuclides

  • We suggested OSEM2D for the calculation of the effective dose of Cu-64 trastuzumab on an Inveon PET scanner

  • We investigated the effect of reconstruction algorithms on the result of image-based dosimetry using Cu-64 trastuzumab PET on a Siemens Inveon PET scanner

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Summary

Introduction

Immuno-PET uses monoclonal antibodies (mAbs) that are labeled with positron-emitting radionuclides. Immuno-PET can be applied for tailored patient management, dose calculation in radioimmunotherapy (RIT), and development of antibody-based drugs [1,2,3]. Cu-64 decays by both β+ (655 keV, 17.4%) and β− (573 keV, 39.0%) emission, making it suitable for both immuno-PET and radioimmuno-therapy (RIT) [4]. The safety of Cu-64 trastuzumab in HER2-positive breast cancer has been investigated using radiation dosimetry [8]. Image-based dosimetry could be used to assess the safety and efficacy of immuno-PET [9,10,11,12]. For the implementation of image-based dosimetry, the cumulative activity (Ã) should be calculated. To calculate the amount of cumulative activity, the region of interest (ROI) was drawn on the reconstructed PET or SPECT data. The dimensions of the matrix, the zoom factors, the spatial filters, and the reconstruction algorithms are factors that determine the spatial resolution of PET [13]

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