Assessment of variability of18F-DCFPyL PSMA PET/CT and PET/MR quantitative parameters from reference standard organs

1315 Objectives: Prostate specific membrane antigen (PSMA)-based radiotracers have shown promise in the setting of prostate cancer. Evaluation of quantitative variability and reproducible reference standards are important for optimal clinical and research utility. In this work, we evaluate the variability of PSMA-based 18F-DCFPyL (PyL) PET quantitative reference standards, including reference sites (liver and parotid gland) proposed in recent PSMA interpretation guidelines.Materials and Methods: Eligible subjects with prostate cancer biochemical recurrence after prostatectomy were prospectively recruited. Approximately 60 minutes after PyL injection, whole body PET/CT (wbPET/CT) from vertex of skull to mid-thigh was obtained on a Discovery 710 PET/CT scanner (General Electric, Waukesha, WI) acquired at 3 minutes per bed position. Subsequently whole body PET/MR (wbPET/MR) was obtained on a Signa PET/MR scanner (GE, Waukesha, WI) acquired at 3 minutes per bed position. Using Mirada XD (Oxford, UK) PET analysis software, two readers independently set a 40% standardized uptake value (SUV) threshold region of interest (ROI) of the whole right parotid gland and separate 1-cm spherical ROIs in the superior, mid, and inferior gland. Additionally, liver and blood pool spherical ROIs were set with 3-cm ROI in the right lobe and 1-cm ROI in the descending aorta, respectively. SUVmean was used for comparison of the quantitative reference standards. Bland-Altman analysis, including bias and limits of agreement (LOA), as well as interquartile range (IQR) was used for statistical analysis. Results: 12 patients were initially included (mean age, 61.8 yrs; range 54-72 years). One patient did not have wbPET/MR and was excluded. Regarding inter-reader variation, there was minimal SUVmean variability (bias±LOA) for blood pool (-0.13±0.42; 0.01±0.41), liver (-0.55±0.82; -0.22±1.3), or whole parotid (-0.05±0.31; 0.080±0.24) for both wbPET/CT and wbPET/MR, respectively. There was greater inter-reader variability for the 1-cm parotid gland ROIs, for both wbPET/CT and wbPET/MR respectively, in all segments; superior (-1.8±5.5; -4.6±11.0), mid (-0.76±2.8; -1.1±3.9), and inferior (-1.4±5.3; -2.7±5.0). Regarding inter-modality variability (bias±LOA for reader 1 and 2, respectively), comparing wbPET/CT to the subsequently acquired wbPET/MR, there was a slight decrease in SUVmean for blood pool (reader 1, -0.59±0.46; reader 2, -0.45±0.46) and a slight increase for liver (reader 1, 0.96±1.1; reader 2, 1.3±1.5) and whole parotid (reader 1, 0.66±1.6; reader 2, 0.77±1.5), although the overall bias was less than 1.5. Inter-subject SUVmean variability on both wbPET/CT and wbPET/MR was much higher for the parotid gland, compared to liver, for both readers. The IQR of whole parotid gland SUVmean was 5.45-6.05 compared to 1.8-2.7 for the liver. Conclusions: Liver and blood pool quantification shows promise as a reliable reference normal organ PSMA PET uptake for clinical and research applications. Whole gland parotid quantification is also promising although it has greater intra-subject variability. In contrast, variable quantification from 1-cm parotid ROIs may limit its use as a reference standard. Figure 1. SUVmean for liver and whole parotid gland ROIs from PyL PET/CT and PET/MR show greater interquartile and min-max range for the parotid gland compared to liver for both reader 1 (figure 1A) and reader 2 (figure 1B). (Box defines median and 1st and 3rd quartiles. Whiskers are maximum and minimum. Diamond defines mean.) Figure 2. (A) Fused coronal PyL PET/CT image with labeled reference organ ROI overlay. (B) PyL PET MIP, from the whole body PET/MR acquisition of the same patient, with overlay of labeled reference organ ROIs. Note the marked spatial variability of the 1-cm ROI SUVmeanis seen in both A and B.