A multicentre and multi-national evaluation of the accuracy of quantitative Lu-177 SPECT/CT imaging performed within the MRTDosimetry project
Authors: Tran-Gia Johannes , Denis-Bacelar Ana M. , Ferreira Kelley M. , Robinson Andrew P. , Calvert Nicholas , Fenwick Andrew J. , Finocchiaro Domenico , Fioroni Federica , Grassi Elisa , Heetun Warda , Jewitt Stephanie J. , Kotzassarlidou Maria , Ljungberg Michael , McGowan Daniel R. , Scott Nathaniel , Scuffham James , Gleisner Katarina Sjögreen , Tipping Jill , Wevrett Jill ,   The MRTDosimetry Collaboration, Bardiès Manuel , Berenato Salvatore , Bilas Ilias , Bobin Christophe , Capogni Marco , Chauvin Maxime , Collins Sean , Cox Maurice , Dabin Jérémie , D’Arienzo Marco , Gustafsson Johan , Hallam Aida , Kalathas Theodoros , Kayal Gunjan , Lorusso Giuseppe , Maringer Franz-Josef , Morgan Darren , Smyth Vere , Šolc Jaroslav , Štemberková Ludmila , Struelens Lara , Vergara-Gil Alex , Wiedner Hannah , Lassmann Michael 
Published: July 2021

Abstract
Purpose
Patient-specific dosimetry is required to ensure the safety of molecular radiotherapy and to predict response. Dosimetry involves several steps, the first of which is the determination of the activity of the radiopharmaceutical taken up by an organ/lesion over time. As uncertainties propagate along each of the subsequent steps (integration of the time–activity curve, absorbed dose calculation), establishing a reliable activity quantification is essential. The MRTDosimetry project was a European initiative to bring together expertise in metrology and nuclear medicine research, with one main goal of standardizing quantitative 177Lu SPECT/CT imaging based on a calibration protocol developed and tested in a multicentre inter-comparison. This study presents the setup and results of this comparison exercise.

Methods
The inter-comparison included nine SPECT/CT systems. Each site performed a set of three measurements with the same setup (system, acquisition and reconstruction): (1) Determination of an image calibration for conversion from counts to activity concentration (large cylinder phantom), (2) determination of recovery coefficients for partial volume correction (IEC NEMA PET body phantom with sphere inserts), (3) validation of the established quantitative imaging setup using a 3D printed two-organ phantom (ICRP110-based kidney and spleen). In contrast to previous efforts, traceability of the activity measurement was required for each participant, and all participants were asked to calculate uncertainties for their SPECT-based activities.

Results
Similar combinations of imaging system and reconstruction lead to similar image calibration factors. The activity ratio results of the anthropomorphic phantom validation demonstrate significant harmonization of quantitative imaging performance between the sites with all sites falling within one standard deviation of the mean values for all inserts. Activity recovery was underestimated for total kidney, spleen, and kidney cortex, while it was overestimated for the medulla.

Conclusion
This international comparison exercise demonstrates that harmonization of quantitative SPECT/CT is feasible when following very specific instructions of a dedicated calibration protocol, as developed within the MRTDosimetry project. While quantitative imaging performance demonstrates significant harmonization, an over- and underestimation of the activity recovery highlights the limitations of any partial volume correction in the presence of spill-in and spill-out between two adjacent volumes of interests.