Repeatability of Quantitative 18F-NaF PET: A Multicenter Study

Abstract

¹⁸F-NaF, a PET radiotracer of bone turnover, has shown potential as an imaging biomarker for assessing the response of bone metastases to therapy. This study aimed to evaluate the repeatability of ¹⁸F-NaF PET-derived SUV imaging metrics in individual bone lesions from patients in a multicenter study.

Methods: Thirty-five castration-resistant prostate cancer patients with multiple metastases underwent 2 whole-body (test-retest) ¹⁸F-NaF PET/CT scans 3 ± 2 d apart from 1 of 3 imaging sites. A total of 411 bone lesions larger than 1.5 cm³ were automatically segmented using an SUV threshold of 15 g/mL. Two levels of analysis were performed: lesion-level, in which measures were extracted from individual-lesion regions of interest (ROI), and patient-level, in which all lesions within a patient were grouped into a patient ROI for analysis. Uptake was quantified with SUV_max, SUV_mean, and SUV_total Test-retest repeatability was assessed using Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation, critical percentage difference, and repeatability coefficient. The 95% limit of agreement (LOA) of the ratio between test and retest measurements was calculated.

Results: At the lesion level, the coefficient of variation for SUV_max, SUV_mean, and SUV_total was 14.1%, 6.6%, and 25.5%, respectively. At the patient level, it was slightly smaller: 12.0%, 5.3%, and 18.5%, respectively. ICC was excellent (>0.95) for all SUV metrics. Lesion-level 95% LOA for SUV_max, SUV_mean, and SUV_total was (0.76, 1.32), (0.88, 1.14), and (0.63, 1.71), respectively. Patient-level 95% LOA was slightly narrower, at (0.79, 1.26), (0.89, 1.10), and (0.70, 1.44), respectively. We observed significant differences in the variance and sample mean of lesion-level and patient-level measurements between imaging sites.

Conclusion: The repeatability of SUV_max, SUV_mean, and SUV_total for ¹⁸F-NaF PET/CT was similar between lesion- and patient-level ROIs. We found significant differences in lesion-level and patient-level distributions between sites. These results can be used to establish ¹⁸F-NaF PET-based criteria for assessing treatment response at the lesion and patient levels. ¹⁸F-NaF PET demonstrates repeatability levels useful for clinically quantifying the response of bone lesions to therapy.

Keywords: PET; metastatic prostate cancer; multicenter clinical trial; repeatability; sodium fluoride.

FIGURE 1.

Whole-body paired baseline ¹⁸F-NaF PET/CT scans of men with metastatic castration-resistant prostate cancer: a 74-y-old imaged 3 d apart at UWCCC (A), a 57-y-old imaged 2 d apart at MSKCC (B), and a 69-y-old imaged 1 d apart at NCI (C).

FIGURE 2.

Box plots of relative differences in each SUV metric (log-transformed) for lesion-level ROIs (left; 411 lesions) and patient-level ROIs (right; 35 patients). Whiskers extend from minimum to maximum values.

FIGURE 3.

Bland–Altman plots of SUV metrics for all lesion-level ROIs (411 lesions): SUV_max (A), SUV_mean (B), and SUV_total (C). Different sites are indicated by different symbols (▪ = UWCCC, ● = MSKCC, and ▲ = NCI). Solid line denotes mean difference, and dotted lines denote upper and lower 95% LOA. Both mean and difference uptake values have been log-transformed.

FIGURE 4.

Bland–Altman plots of SUV metrics for all patient-level ROIs (35 patients): SUV_max (A), SUV_mean (B), and SUV_total (C). Different sites are indicated by different symbols (▪ = UWCCC, ● = MSKCC, and ▲ = NCI). Solid line denotes mean difference, and dotted lines denote upper and lower 95% LOA. Both mean and difference values have been log-transformed.

FIGURE 5.

Overall ICC plotted against overall coefficient of variation of lesion-level (black) and patient-level (red) SUV metrics.

FIGURE 6.

Bland–Altman plots of lesion SUV_max by site: UWCCC (265 lesions) (A), MSKCC (78 lesions) (B), and NCI (68 lesions) (C). Each point represents a lesion, and different subjects are indicated by different colors. Solid lines denote site-specific mean difference, and dotted lines denote site-specific upper and lower 95% LOA. Both mean and difference uptake values have been log-transformed.