Pitfalls in Gallium-68 PSMA PET/CT Interpretation-A Pictorial Review

Abstract

The novel Gallium-68 prostate-specific membrane antigen (PSMA)-bis [2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-diacetic acid positron emission tomography (PET) tracer is increasingly used in the evaluation of prostate cancer, particularly in the detection of recurrent disease. However, PSMA is expressed in nonprostatic tissues, as well as in other pathologic conditions. Here we illustrate such interpretive pitfalls with relevant images that one may encounter while reporting PSMA PET/CT. This study aims to show variation in physiological distribution of PSMA activity and uptake in various benign and neoplastic disorders that may be misinterpreted as prostatic metastatic disease. These pitfalls are illustrated to enhance awareness, aiding a more accurate interpretation of the study. Retrospective database of all (68)Ga PSMA PET/CT was created and reviewed. In total, 1115 PSMA PET/CT studies performed between February 27, 2015, and May 31, 2017, were reviewed. Any unusual uptake of PSMA was documented, described, and followed up. All cases were then subdivided into the following 4 categories: physiological uptake, benign pathological uptake, nonprostatic neoplastic uptake, and miscellaneous uptake. A variety of nonprostatic tissues and lesions, including accessory salivary gland, celiac ganglion, gall bladder, Paget's bone disease, reactive lymph nodes, non-small cell lung cancer, renal cell cancer, and neuroendocrine tumor, were found to show PSMA uptake. PSMA uptake is not prostate-specific and can be taken up physiologically and pathologically in nonprostatic tissue. It is important for reporting physicians to recognize these findings and instigate appropriate investigations when required while avoiding unnecessary procedures in physiological variation.

Keywords: Ga 68 PSMA PET/CT; pitfalls; prostate cancer.

Figure 1.

Anterior reprojection emission prostate-specific membrane antigen (PSMA) positron emission tomography (PET) image from skull vertex to knees showing the normal distribution of the PSMA tracer. Intense activity is seen in the kidneys with moderate activity in the lacrimal glands, salivary glands, liver, spleen, proximal small bowel, and urinary bladder. The injection site in the left cubital fossa shows marked activity.

Figure 2.

Axial PSMA PET/low-dose computed tomography (CT) fused image showing symmetrical (A) and asymmetrical PSMA (B) uptake in the right submandibular gland, while the left submandibular gland is not visible in a different patient, which may be due to atrophy or agenesis. Axial PSMA PET/CT-fused (C) and CT (D) images showing marked PSMA uptake in the right accessory parotid gland, which is usually located on the masseter muscle. Concurrent low-dose CT image showing a small low-density soft tissue similar in attenuation to the parotid gland.

Figure 3.

Axial PET image (A) and PET/CT-fused (B) image showing mild uptake in the left celiac ganglion, which appears as an elongated discoid structure anterolateral to the abdominal aorta. Axial PET (C) and PET/CT-fused (D) image showing moderate, diffuse PSMA uptake in the gall bladder, which shows normal configuration on concurrent PET/CT image.

Figure 4.

Axial low-dose CT (A) and PET/CT-fused (B) images showing mild uptake at the right pulmonary hilum corresponding to nonenlarged soft tissue/lymph node. Axial low-dose CT (C) and PET/CT-fused (D) images showing mild uptake in a nonenlarged left axillary lymph node.

Figure 5.

Axial low-dose CT (A) and PET/CT-fused (B) images showing moderate PSMA uptake in the longstanding and stable pleural plaques along the right posterior pleura; the patient had multiple bilateral calcified and noncalcified pleural plaques consistent with the history of asbestos exposure.

Figure 6.

Low dose CT (A) shows Pagetoid changes (thickened cortex, coarsened trabeculae and expanded bone) but mild patchy PSMA uptake is seen in the right ilium on PET/CT (B).

Figure 7.

Mild focal PSMA activity at the site of healing fracture in the anterior aspect of the left fifth rib (A and B). Mild diffuse uptake (D) is seen in a large osteophyte lipping of L5/S1 discovertebral joint (C). Osteoarthritic changes in the hips bilaterally (E) show patchy mild PSMA uptake (F).

Figure 8.

Low-dose CT (A) and PET/CT-fused (B) image showing intense PSMA activity at the costochondral junction corresponding to a small sclerotic focus at the head and neck of the left fifth rib.

Figure 9.

Axial PET (A), PET/CT-fused (B), and anterior reprojection emission PET image (C) showing mild, diffuse PSMA activity in the axial and proximal appendicular skeleton in a patient with known polycythemia rubra vera.

Figure 10.

Low-dose CT in lung windows (A) and PET/CT-fused (B) images showing intensely avid PSMA uptake in a case of non–small cell lung cancer recurrence in the lingular lobe. PET/CT-fused (C) and PET (D) images showing mildly increased PSMA uptake in the gastric cardia in a case of high-grade invasive gastric adenocarcinoma. Diffuse rectal wall thickening is shown on a low-dose CT (E) corresponding to mild, diffuse, increased PSMA uptake (F). Further evaluation with biopsy and histopathology assessment revealed a primary rectal malignancy.

Figure 11.

Low-dose CT (A) and fused PET/CT (B) images showing mild heterogeneously increased PSMA uptake in a mass arising from the right kidney that was identified to be renal cell carcinoma after histopathology assessment. An intensely PSMA avid, arterially enhancing pancreatic nodule was incidentally detected during PSMA PET/CT study performed for staging of prostate cancer, as seen in fused PET/CT (C) and PET (D), which was confirmed as neuroendocrine tumour by histopathology.

Figure 12.

Incidental large, intensely PSMA-avid lesions are seen in the liver, showing arterial enhancement with central washout in venous phase on triple-phase CT as well as magnetic resonance imaging (not shown in the images here). CT-guided core biopsy was performed, and histopathology confirmed well-differentiated hepatocellular carcinoma (A–D) (32).

Figure 13.

PSMA-PET/CT showing mild-to-moderate increase in nodular uptake in an enlarged right thyroid gland (A–B).

Figure 14.

A small mildly sclerotic lesion in the right posterior aspect of the vertebral body was found to be minimally PSMA-avid (A and B) and therefore suspicious for prostatic metastases; however, no corresponding osteoblastic activity on bone scan was identified in the lesion (C).

Figure 15.

Fused PET/CT (A) and anterior maximum intensity projection image (B) in a gynecomastia demonstrate increased PSMA uptake, thought to be related to antiandrogen therapy for prostate cancer demonstrates mild diffuse symmetrical PSMA activity.

Figure 16.

Low-dose CT (A) does not demonstrate any abnormality, at the location of mild asymmetrical PSMA uptake detected in the lower portion of the rectus abdominis (B) likely related to physical activity/trauma.

Figure 17.

Fused PET/CT (A) and PET (B) demonstrate atelectasis of the right posterior lung base showing PSMA activity. There is absent uptake at the location of a small right effusion. Faint PSMA activity is also noted at mild atelectasis and and pleural thickening along the posterior and lateral aspect of the left hemithorax (A and B).

Figure 18.

Low dose CT (A) and fused PET/CT (B) show intense activity in the urinary bladder can mask a PSMA avid soft-tissue mass adjacent to the right anterolateral aspect of the urinary bladder which invades the bladder wall. Fused PET/CT (C) and PET (D) demonstrate another example of a PSMA avid sclerotic lesion which can be missed during the initial review due to adjacent PSMA urinary activity in the urinary bladder.