A Quick Guide for Better Image Quality & Accurate Interpretation

With PSMA PET/CT playing an increasingly critical role in guiding prostate cancer treatment decisions, the accurate execution and interpretation of these scans have never been more important. Drawing from decades of experience and thousands of PSMA PET/CT scans we have evaluated, we have compiled a practical guide highlighting the most common pitfalls – and how to avoid them.

Before the Scan (Patient Scheduling, Pre-Treatment Timing, Patient Preparation)

1. Non-optimal time window due to pre-treatments: Best timing is before long-term ADT or chemotherapy to avoid downregulation of PSMA expression; alternatively, use short-term ADT (2–4 weeks) for flare/upregulation to enhance detection. Scanning too soon or too late relative to therapy can reduce sensitivity or lead to misinterpretation.
2. Poor timing due to tracer half-life: Ga-68 has a short half-life (68 minutes), requiring precise scheduling from production to injection and scanning; delays can reduce activity and image quality. F-18 (half-life ~110 minutes) allows more flexibility but still demands coordination for delivery and patient preparation.
3. Using inconsistent equipment or protocols (planning/setup aspect): Variations in scanners, overall protocols (e.g. no forced diuresis before acquiring delayed images of the pelvis for local recurrence or disease), or lack of standardized pre-scan instructions introduce bias and reduce comparability (especially Ga-68 vs. F-18 comparisons).

During the Scan (Tracer Handling, Instructions, Injection, Uptake, Positioning, Acquisition, Intra-Procedure Interventions)

4. Inaccurate dose calibration: Especially for Ga-68, errors in calibrating the dose can lead to inaccurate quantitative measurements (e.g. SUV values), reducing sensitivity for small tumors.
5. Encourage hydration: Failing to instruct the patient to stay well-hydrated (e.g. drink sufficient water before arrival and continue during the ~60-min uptake/waiting period) increases urinary activity and artifacts.
6. Failing to use diuretics or ensure voiding: Not administering furosemide or having the patient void immediately before imaging (joint EANM/SNMMI procedure guidelines for PSMA PET/CT^[1]) to reduce physiologic activity in the urinary system exacerbates urinary excretion artifacts, particularly with ⁶⁸Ga-PSMA-11, leading to halo artifacts (unwanted distortions) around kidneys and bladder that obscure nearby lesions. This is less problematic with ¹⁸F-PSMA-1007 due to lower urinary excretion but can still affect detection rates if ignored.
7. Not accounting for patient motion: Respiratory or voluntary movement causes misregistration between PET and CT images, particularly near the diaphragm or extremities, distorting lesion localization. Instructions to remain still and breath-hold techniques can mitigate this.

Interpreting PSMA PET/CT Scans

Interpretation errors often stem from unfamiliarity with normal biodistribution, variants, and non-specific uptake, leading to false positives or negatives. Mistakes vary slightly between Ga-68 and F-18 tracers.

General Interpretation Mistakes (Applicable to Both Ga-68 and F-18)

1. Misinterpreting normal physiological uptake as metastasis: Low-grade uptake in sympathetic ganglia (e.g. celiac, stellate), salivary glands, pancreas, or duodenum can be confused with lymph node or organ metastases if not correlated with CT morphology and location.
2. Overlooking artifacts: Halo artifacts from intense renal/bladder activity (more with Ga-68) cause photopenic areas, potentially missing peri-renal lesions; motion artifacts lead to misaligned images.
3. False negatives in PSMA-low tumors: Certain aggressive cancers and metastases show low PSMA expression, leading to non-avid primaries or metastases, especially after chemotherapy; consider alternative tracers like FDG or FAPi in biochemical recurrence.
4. False positives from inflammation or benign conditions: Uptake in prostatitis, fractures, osteophytes, Paget's disease, or infections (e.g. tuberculosis) can mimic metastases.
5. Confusing non-prostate malignancies: PSMA uptake in other cancers (e.g. renal cell carcinoma, lymphoma, neuroendocrine tumors) due to neovascularization.

Specific to ⁶⁸Ga-PSMA

1. Underestimating urinary interference: Higher urinary excretion can obscure local recurrences near the bladder; furosemide & delayed pelvic imaging post-voiding helps.

Specific to ¹⁸F-PSMA

1. Overinterpreting benign bone uptake as metastases: Higher SUV in benign bone lesions leads to false positives (up to 6 times more unspecified uptake than Ga-68).
2. Missing lesions due to liver uptake: Intense hepatic activity obscures adjacent metastases (e.g. adrenal or bone).
3. Misreading ganglia uptake: Greater uptake in benign ganglia can be mistaken for lymph node metastases.

Download a quick guide here: PSMA PET CT Common Pitfalls & How To Avoid Them

^[1]Fendler WP, Eiber M, Beheshti M, Bomanji J, Calais J, Ceci F, Cho SY, Fanti S, Giesel FL, Goffin K, Haberkorn U, Jacene H, Koo PJ, Kopka K, Krause BJ, Lindenberg L, Marcus C, Mottaghy FM, Oprea-Lager DE, Osborne JR, Piert M, Rowe SP, Schöder H, Wan S, Wester HJ, Hope TA, Herrmann K. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging. 2023 Apr;50(5):1466-1486. doi: 10.1007/s00259-022-06089-w. Epub 2023 Jan 5. PMID: 36604326; PMCID: PMC10027805.