Nonspecific uptake of ⁶⁸Ga-prostate-specific membrane antigen in diseases other than prostate malignancy on positron emission tomography/computed tomography imaging: A pictorial assay and review of literature

Abstract

68Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography imaging (PET/CT) is a rapidly evolving imaging modality for prostate cancer. Many studies have proved its superiority in staging, restaging, and detecting the recurrent prostate cancer. However, case reports describing the incidental tracer uptake in benign and nonprostatic malignancies are also reported in the literature, thus questioning the specificity of the tracer. This pictorial assay illustrates the nonspecific tracer uptake encountered during PSMA PET/CT imaging, knowledge of which can increase the confidence of interpreting physicians and may also open a new path for peptide receptor radionuclide therapy in nonprostatic malignancies.

An overview on prostate-specific membrane antigen uptake in malignancies other than prostate cancer: A pictorial essay

“…[ 2 ] Although PSMA first was identified in the prostate gland, its expression in the duodenal epithelium, proximal tubule cells in the kidney, salivary glands, and tumor-associated vascular endothelium have been revealed in eventual histopathological studies. [ 3 4 5 ]…”

“…However, despite its name, in addition to prostate tissue, PSMA is physiologically expressed in a multiple number of nonprostatic malignancies because of PSMA mRNA transcripts and protein expression in the endothelium of tumor-related neovasculature, leading to potential pitfalls in the clinical use of PSMA-targeted imaging. [ 3 4 15 ] Nevertheless, PSMA expression in nonprostatic malignancies may prove beneficial in therapeutic and imaging targets for these conditions. Table 1 represents malignancies other than prostate cancer which shows PSMA uptake in previous researches.…”

PSMA Uptake in a Subdural Hematoma

“…The primary binding target for PSMA PET radiopharmaceuticals is the PSMA, a type II transmembrane glycoprotein overexpressed in prostate cancer cells. 1 Despite its name, PSMA expression has been shown in a variety of other nonprostatic tumor cells and associated neovasculature including glioblastoma, 2 renal cell carcinoma, 3 and hepatocellular carcinoma. 4 PSMA uptake has also been described in nonmalignant processes such as within lung consolidation from increased capillary permeability, 1 as well as Paget disease, which is thought secondary to osteoblastic activity.…”

“…10 Normal brain parenchyma shows a complete absence of PSMA radiotracer uptake secondary to an intact blood-brain barrier that the radiopharmaceutical does not normally cross. 1 Nonspecific 68 Ga-PSMA radiotracer activity has previously been described within cerebral infarcts and hemorrhages, which is thought secondary to disruption of the blood-brain barrier. 1 This is likely the mechanism of uptake in our example: the radiotracer entered the collection via the bloodstream and distributed throughout the collection, without specific receptor binding.…”

“…1 Nonspecific 68 Ga-PSMA radiotracer activity has previously been described within cerebral infarcts and hemorrhages, which is thought secondary to disruption of the blood-brain barrier. 1 This is likely the mechanism of uptake in our example: the radiotracer entered the collection via the bloodstream and distributed throughout the collection, without specific receptor binding. This case emphasizes the importance of reviewing the CT and PET images for sites of primary disease, as well as other incidental findings, which can be life-threatening.…”