¹⁸F-FDG PET/CT is widely used in the management of multiple myeloma (MM), a disease that often presents with extensive bone involvement. Radiolabeled prostate-specific membrane antigen (PSMA), primarily a marker for prostate cancer, is also associated with tumor neoangiogenesis, and studies have demonstrated its uptake in MM lesions. Hybrid PET/CT imaging with both FDG and PSMA tracers allows for several quantitative metrics, enabling objective comparisons beyond visual analysis.

This study aims to compare ¹⁸F-FDG and ⁶⁸Ga-PSMA PET/CT quantitative metrics in the skeletal system of patients with MM.

The study included ¹⁸F-FDG and ⁶⁸Ga-PSMA PET/CT images acquired within a 1- to 8-day interval from 15 patients (53% male, mean age 66.7 ± 10.7 years) with symptomatic, biopsy-proven MM. CT was used to segment the entire skeleton in PET images, with the skull excluded in ¹⁸F-FDG images due to artifacts from brain uptake coregistration. SUV quantification was performed using in-house software developed in MATLAB. Descriptive statistics and individual percentage deviations between the radiotracers were used to evaluate bone mean and maximum Standardized Uptake Values (SUVmean and SUVmax). Correlation analysis between the radiotracers was conducted using Spearman's rank correlation coefficient (r) with a significance level of p < 0.05.

For bone SUVmean, values were higher for ¹⁸F-FDG compared to ⁶⁸Ga-PSMA, with an average of 0.9 ± 0.1 vs. 0.5 ± 0.1, corresponding to a -40% ± 9% difference (range: -25% to -57%). Conversely, for bone SUVmax, values were lower for ¹⁸F-FDG compared to ⁶⁸Ga-PSMA, with an average of 8 ± 3 vs. 19 ± 14, corresponding to a 154% ± 2% difference (range: -21% to 762%). A moderate correlation was found for bone SUVmean between ¹⁸F-FDG and ⁶⁸Ga-PSMA (r = 0.55, p = 0.03), while no significant correlation was observed for bone SUVmax (r = 0.17, p = 0.55).

This study reveals distinct quantitative uptake patterns between ¹⁸F-FDG and ⁶⁸Ga-PSMA PET/CT in the skeletal system of MM patients. ¹⁸F-FDG exhibited significantly higher SUVmean than ⁶⁸Ga-PSMA, likely due to physiological ¹⁸F-FDG uptake in bone marrow. A moderate correlation was observed for SUVmean between the two tracers. The higher SUVmax values for ⁶⁸Ga-PSMA, with no correlation with ¹⁸F-FDG SUVmax, may reflect the different biological targeting mechanisms of each tracer. This suggests that some regions of increased PSMA uptake (possibly indicating neoangiogenesis) may not correspond to areas of increased glycolysis, highlighting the potential complementary role of these radiotracers in MM evaluation.