Normal Variants, Pitfalls, and Artifacts in Ga-68 Prostate Specific Membrane Antigen (PSMA) PET/CT Imaging

Abstract

The advent of gallium 68 prostate specific membrane antigen (PSMA) PET imaging has revolutionized the diagnosis and treatment of prostate cancer. PSMA is a transmembrane glycoprotein that is overexpressed in prostate cancer and yields images with high tumor-to-background contrast. Effective “one-stop-shop” imaging of the prostate, lymph nodes, soft tissue, and bone is achieved with PSMA PET. Compared to conventional imaging, PSMA PET provides superior sensitivity and specificity and plays a pivotal role in staging high-risk prostate cancer as well as in biochemical recurrence by identifying oligometastatic disease. PSMA PET furthermore assists in the selection of patients with metastatic castrate resistant prostate cancer for possible treatment (e.g., labeled with a beta emitter lutetium 177) by using a theranostic approach. The term “prostate specific” is a misnomer as PSMA is also present in other malignant and benign conditions since it acts as a folate hydrolase. To avoid pitfalls and false-positives, a sound knowledge of the normal biodistribution of PSMA as well as other potential causes for false-positive uptake is imperative. This review will describe the expected patterns of distribution of Ga 68 PSMA PET imaging and the common pitfalls noted in published literature since the topic is still evolving.

Primary Staging of Prostate Cancer Patients with [18F]PSMA-1007 PET/CT Compared with [68Ga]Ga-PSMA-11 PET/CT

“…The reasons for reduced specificity in PSMA imaging are well known and include neovascularization and PSMA overexpression in non-prostatic tissue, e.g., benign neoplasms, i.e., thyroid and parathyroid adenomas, and in non-prostatic malignancies such as breast cancer, thyroid cancer, gliomas, lung cancer, neuroendocrine tumors, lymphoma, and renal cell carcinoma. There are fewer false positives if the PSMA images are interpreted by experts who are aware of the various pitfalls [ 16 ].…”

Intense prostate-specific membrane antigen receptor expression in coronary artery pypass graft scar tissue: A potential molecular imaging pitfall

“… 4 Compared to traditional imaging methods, 68 Ga-PSMA PET/CT demonstrates higher levels of sensitivity and specificity, making it a valuable tool in the staging of high-risk prostate cancer and the detection of oligometastatic disease during biochemical recurrence. 16 This is not applicable in all scenarios; for example, the specificity of 68 Ga-PSMA PET/CT tends to be underwhelmed by various pitfalls that become increasingly unraveled with time. Inflammatory and infective conditions can mimic PSMA-avid lesions, but these can often be distinguished based on morphologic criteria seen on CT images.…”

Prostate-Specific Membrane Antigen PET-CT Imaging for the Staging of Prostate Cancer in Canada

“…5 PSMA is also expressed in the blood vessels of many solid tumours. 5 Both gallium-68 (68Ga) and fluorine-18 (18F)-labelled PSMA-specific radiopharmaceuticals are clinically used to stage prostate cancer tumour cells with PET-CT. 6 A growing body of evidence [6][7][8][9] suggests that PSMA-directed PET (PSMA-PET) radiopharmaceuticals can determine different stages of cancer in the prostate with more specificity than conventional imaging such as CT, MRI, and bone scan, 10 and can detect spread to pelvic nodal or distant metastatic sites. 11 Accurate staging of prostate cancer before primary therapy can help guide treatment decisions, such as choices between surgery and radiation therapy, use of adjuvant hormone therapy, and design of therapeutic approaches, such as targeting suspicious lymph nodes for node dissection or radiotherapy.…”