Multicenter Comparison of Radionuclide Calibrators and SPECT/CT Protocols for Quantitative 177Lu Imaging in Clinical Practice

TL;DR

This multicenter phantom study addresses inter-center variability in quantitative Lu-177 imaging by evaluating end-to-end performance of radionuclide calibrators (RNCs) and SPECT/CT across eight hospitals and 13 scanners. By using traceable vials and two phantoms (cylinder and NEMA IQ) under site-specific and standardized protocols, the study quantifies image calibration factors (ICFs) and recovery coefficients (RCs) to assess SPECT quantitative accuracy. Results show up to 11% spread in RNC readings, up to 20% variability in cylinder RCs, and up to 58% in NEMA RCs, with standardized reconstructions significantly reducing inter-system variability within the same scanner family but inter-family differences (conventional vs CZT) persisting. The findings support harmonization centered on standardized calibration against traceable references and standardized reconstruction settings to enhance multicenter comparability of quantitative Lu-177 SPECT/CT, while acknowledging ongoing challenges in cross-type harmonization.

Abstract

Purpose: Following the clinical success of 177Lu-based therapies for neuroendocrine tumors and prostate cancer, accurate quantification of 177Lu using radionuclide calibrators (RNCs) and 177Lu-SPECT/CT is gaining importance as prerequisite for accurate treatment delivery and dosimetry. However, the lack of standardization can introduce inter-system variability, compromising multi-center clinical trials. This study aimed to assess the accuracy and variability of 177Lu measurements using RNCs and SPECT/CT across different systems and hospitals. Methods: A uniform cylindrical phantom and a NEMA phantom with hot spheres were prepared using traceable activities and imaged at 8 different hospitals using 13 SPECT/CT systems (9 conventional and 4 3D CZT). Acquisitions and reconstructions were performed using both site-specific and standardized protocols. The cylindrical phantom images were used to establish image calibration factors (ICFs), the NEMA images to evaluate image quality by calculating recovery coefficients (RCs). Both were used to evaluate quantitative SPECT accuracy. In parallel, two vials were measured to test RNC accuracy. Results: RNC measurements differed up to 11% between centers, while SPECT quantification differed up to 20% and 58% for the cylindrical and NEMA phantoms respectively. While ICFs were consistent for systems of the same type, image quality varied strongly when using clinical protocols. Standardized reconstruction reduced variability for each system type, regardless of acquisition protocol, but differences between system types persisted when harmonizing acquisition and reconstruction. Conclusion: Current 177Lu measurement practices yield significant variability in quantification and image quality. Harmonization efforts should prioritize standardized calibration and reconstruction protocols to improve multicenter reproducibility of quantitative 177Lu-SPECT/CT.

Figures (18)

• Figure 1: Deviations of the activities measured by the different RNCs using the factory protocol. The dotted lines indicate the 95% confidence interval of the reference activity.
• Figure 2: Deviations of the activities measured by the different RNCs using the clinical protocol. The dotted lines indicate the 95% confidence interval of the reference activity. The upper and lower values for RNC F were obtained using the DOTATATE and PSMA settings respectively.
• Figure 3: Deviations of the activities reported by the sites, using their own SPECT calibration factors, from the activity obtained with the gamma counter for 8 SPECT/CT systems. The dashed and dotted lines indicate the 95% confidence intervals for the reference activity in the cylinder and NEMA phantom, respectively.
• Figure 4: Image calibration factors (ICFs) for the conventional Siemens Symbia and GE Discovery systems and the CZT-based GE StarGuide system.
• Figure 5: Recovery curves for the different systems using the different protocols. Blue: Siemens Symbia (n=5); red: GE Discovery (n=4); purple: GE Starguide (n=2); orange: Spectrum Dynamics Veriton (n=2). Since the standardized acquisition protocol could only be applied to conventional systems, no fully standardized curves for the CZT systems are shown.