Performance evaluation of a preclinical SPECT system and optimization of imaging protocols for 177Lu-labelled radiopharmaceuticals

This study investigates the performance of the γ-CUBE preclinical SPECT scanner to optimize acquisition and reconstruction protocols for theranostic preclinical studies, and to determine the minimum administered activity of a novel 177 Lu-labelled peptide in a mouse cancer model without compromising image quality. System performance was evaluated in terms of uniformity, spatial resolution and contrast-to-noise ratio (CNR) using syringes and Derenzo phantoms, comparing 177 Lu with 99m Tc. Three interchangeable collimators (general-purpose-rat (GP-R), general-purpose-mouse (GP-M) and high-sensitivity-mouse (HS-M)) were tested by varying the number of iterations of the reconstruction algorithm. Quantitative accuracy for 177 Lu was determined at 50 iterations using a biomimetic mouse phantom and polypropylene tubes filled with activity concentrations ranging from 0.095 to 2.36 MBq/ml. Threshold injection activity was estimated in three tumour-bearing mice injected with 16.0 ± 1.3 MBq of 177 Lu-labelled peptide and scanned with HS-M collimator at different time points post-injection. Lower activities (1.6–12 MBq) were simulated by retrospective reconstructions. Tumour CNR at 48 and 168 h post-injection was calculated, and image quality was assessed by five independent readers using a 5-point scale. Integral uniformity with 99m Tc was 18.3% (GP-R), 23.6% (GP-M) and 17.3% (HS-M) at 50 iterations. Increasing iterations degraded uniformity, with 99m Tc consistently showing superior values compared to 177 Lu. GP-M collimator resolved all Derenzo rods (down to 1 mm) for both radionuclides, HS-M resolved rods ≥ 1.6 mm at 500 iterations and GP-R collimator resolved rods ≥ 1.4 mm for 99m Tc and ≥ 2 mm for 177 Lu at 500 iterations. The HS-M collimator provided superior quantitative accuracy (> 90%) for all tested activity concentrations. Tumour CNR worsened with reducing injected activity. 8 MBq was identified as the threshold to obtain good image quality up to 7 days post-injection, while 4 MBq was acceptable for short-term studies (< 48 h). The γ-CUBE system offers versatile performance for imaging with both 99m Tc and 177 Lu. The HS-M collimator is recommended for low-activity studies, and 50 iterations represents the best compromise for routine applications. Optimization analysis confirmed that in the experimental paradigm used for the study the injected activity of 177 Lu-peptide can be significantly reduced while maintaining adequate image quality for longitudinal biodistribution studies.