Preferred Reference Organ for F-18 PSMA PET Scans
The parotid gland is the preferred reference organ for F-18 PSMA PET scan interpretation, based on its superior test-retest repeatability and established use in standardized reporting frameworks.
Primary Reference Organ: Parotid Gland
The parotid gland demonstrates the highest repeatability for F-18 PSMA tracers and serves as the standard reference in clinical practice. 1, 2
For F-18 DCFPyL (a widely used F-18 PSMA tracer), the parotid gland shows excellent test-retest repeatability with a within-subject coefficient of variation (wCOV) of only 9.0-14.3% for SUVmean measurements 1
The whole parotid gland (using a 40% SUV threshold ROI) demonstrates minimal inter-reader variability with bias±limits of agreement of -0.05±0.31 for PET/CT and 0.08±0.24 for PET/MR 2
Standardized frameworks for PSMA scan interpretation (PROMISE criteria) specifically rely on parotid gland uptake as the reference standard 1
Practical Implementation
Use the entire parotid gland rather than small 1-cm regions of interest for optimal reproducibility. 1, 2
Whole parotid gland measurements show superior repeatability compared to smaller 1-cm spherical ROIs within the gland 1, 2
Small ROIs in the parotid demonstrate greater inter-reader variability (wCOV 12.4% for submandibular, 23.9% for lacrimal glands) 1
The parotid gland provides higher tumor-to-background ratios compared to other reference organs when evaluating F-18 PSMA lesions 3
Alternative Reference Organs
The liver serves as an acceptable alternative reference organ, particularly for quantitative assessments. 1, 2
Liver SUVmean demonstrates high repeatability (wCOV 9.0-14.3%) comparable to the parotid gland 1
Right hepatic lobe measurements show minimal inter-reader variability (bias±LOA of -0.55±0.82 for PET/CT) 2
However, tumor-to-liver ratios may not show significant differences compared to tumor-to-parotid ratios for F-18 PSMA tracers 3
Blood pool (mediastinum) can be used but shows slightly lower repeatability. 1, 2
Blood pool SUVmean has acceptable repeatability with minimal inter-reader variability (bias±LOA -0.13±0.42) 2
Tumor-to-mediastinum ratios do not show significant advantages over parotid-based ratios for F-18 PSMA imaging 3
Clinical Significance
The parotid gland reference is particularly important for predicting response to PSMA-targeted radioligand therapy. 4
The PSMA PET tumor-to-salivary gland (PSG) score using parotid uptake as reference predicts treatment response and overall survival after Lu-177 PSMA therapy 4
Patients with high PSG scores (tumor uptake > 1.5 times parotid uptake) show significantly better PSA response rates (69.6% vs 38.7% vs 16.7% for high vs intermediate vs low groups, P<0.001) 4
Visual assessment of tumor uptake relative to parotid glands demonstrates substantial inter-reader reproducibility (Fleiss weighted κ = 0.68) 4
Common Pitfalls to Avoid
Avoid using small ROIs or submandibular/lacrimal glands as primary references due to higher variability. 1, 2
Submandibular and lacrimal glands show significantly higher inter-reader and test-retest variability compared to parotid glands 1
SUVmax measurements in reference organs generally show lower repeatability than SUVmean measurements (wCOV range 14.1-45.2% for large organs) 1
Be aware that inter-subject variability is inherently higher for parotid glands compared to liver or blood pool, but this does not affect its utility as a reference standard. 2