Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin, a novel Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that ofLu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

We evaluated the performance characteristics of a prototype preclinical PET scanner available as an easy clippable assembly that can dock to an MRI system. The single ring version of the PET system consists of eight detectors, each of which comprises a 12  ×  12 silicon photomultipliers (SiPMs) array coupled with a dual layer of offset scintillation crystals to measure depth of interaction. The crystal arrays have 29  ×  29 (30  ×  30 for the outer layer) 4 mm long LYSO crystals (6 mm for the outer layer). The ring diameter is 119.2 mm and the axial field of view is 50.4 mm. The NEMA NU 4-2008 protocol was followed for studying the PET performance. Temperature stability of SiPMs was also investigated. The peak system absolute sensitivity was 4.70% with an energy window of 250-750 keV. The spatial resolution was 1.28/1.88/1.85 mm FWHM (radial/tangential/axial) at a distance of 5 mm from the center. Peak noise equivalent counting rate and scatter fraction for mouse phantom were 61.9 kcps at 14.9 MBq and 21.0%, respectively. The uniformity was 6.3% and the spill-over ratios in the images of the water-and air-filled chambers were 0.07 and 0.17, respectively. Recovery coefficients ranged from 0.13 to 0.96. Change in sensitivity as a function of ambient temperature was 0.3%/°C. These first results indicate excellent spatial resolution performance for use with animal studies. Moreover, the clippable assembly can be upgraded to accept a second ring of SiPMs modules, leading to improved sensitivity and axial coverage.

We present the design and performance of a new compact preclinical system combining positron emission tomography (PET) and magnetic resonance imaging (MRI) for simultaneous scans. The PET contains sixteen SiPM-based detector heads arranged in two octagons and covers an axial field of view (FOV) of 102.5 mm. Depth of interaction effects and detector's temperature variations are compensated by the system. The PET is integrated in a dry magnet operating at 7 T. PET and MRI characteristics were assessed complying with international standards and interferences between both subsystems during simultaneous scans were addressed. For the rat size phantom, the peak noise equivalent count rates (NECR) were 96.4 kcps at 30.2 MBq and 132.3 kcps at 28.4 MBq respectively with and without RF coil. For mouse, the peak NECR was 300.0 kcps at 34.5 MBq and 426.9 kcps at 34.3 MBq respectively with and without coil. At the axial centre of the FOV, spatial resolutions expressed as full width at half maximum / full width at tenth maximum (FWHM/FWTM) ranged from 1.69/3.19 mm to 2.39/4.87 mm. The peak absolute sensitivity obtained with a 250-750 keV energy window was 7.5% with coil and 7.9% without coil. Spill over ratios of the NEMA NU4-2008 image quality (NEMA-IQ) phantom ranged from 0.25 to 0.96 and the percentage of non-uniformity was 5.7%. The image count versus activity was linear up to 40 MBq. The principal magnetic field variation was 0.03 ppm/mm over 40 mm. The qualitative and quantitative aspects of data were preserved during simultaneous scans.