PSMA Expression in Solid Tumors beyond the Prostate Gland: Ready for Theranostic Applications?

Abstract

In the past decades, the expanding use of prostate-specific membrane antigen (PSMA) imaging for prostate cancer has led to the incidental detection of a lot of extra-prostatic malignancies showing an increased uptake of PSMA. Due to these incidental findings, the increasing amount of immunohistochemistry studies and the deeper knowledge of the mechanisms of expression of this antigen, it is now clear that “PSMA” is a misnomer, since it is not specific to the prostate gland. Nevertheless, this lack of specificity could represent an interesting opportunity to bring new insights on the biology of PSMA and its sites of expression to image and treat new conditions, particularly several cancers. In this review, we will describe the main extra-prostatic cancers that exhibit PSMA expression and that can be studied with PSMA-based positron emission tomography–computed tomography (PET/CT) as an additional or alternative tool to conventional imaging. In particular, we will focus on cancers in which a radioligand therapy with 177lutetium has been attempted, aiming to provide an overview of the possible future theragnostic applications of PSMA.

Comparison of 68Ga-PSMA-HBED-CC and 18F-FDG PET/CT in the Evaluation of Adenoid Cystic Carcinoma—A Prospective Study

“…9 Morphological anatomy is well established in CT and MRI, but these modalities have a limited role in differentiating between fibrosis and viable tumor in postoperative/RT cases. 24 Over the past decade, several studies have shown that PSMA is expressed by a number of malignant tumors other than prostate such as sarcoma, follicular lymphoma, brain tumors, and carcinoma of the breast, lung, kidney, thyroid, and liver. [17][18][19] PSMA, labeled with 68 Ga and 177 Lu, has been used for diagnostic and therapeutic purpose.…”

“…However, guidelines of clinical management and treatment of metastatic AdCC are not well established 9 . Morphological anatomy is well established in CT and MRI, but these modalities have a limited role in differentiating between fibrosis and viable tumor in postoperative/RT cases 24 …”

Recent Pre-Clinical Advancements in Nuclear Medicine: Pioneering the Path to a Limitless Future

“…In addition to its role in PC, PSMA overexpression has been identified in various other tumor types, such as glioblastoma or hepatocellular carcinoma (HCC), making them potential candidates for 68 Ga-PSMA-11 imaging and 177 Lu-PSMA-617 treatment [53]. Pilot studies in patients with HCC demonstrated significant uptake in seven patients with multiple liver lesions.…”

Intense 18F–Prostate-Specific Membrane Antigen Uptake and Mild 18F-FDG Uptake in a Biopsy-Proven Pulmonary Hemangioma

“…Histology after surgical resection reveals a hemangioma. Focal intense PSMA activity in a lung lesion is suggestive of metastatic disease from prostate cancer; however, a variety of benign and nonprostatic neoplasms have demonstrated increased PSMA expression that leads to abnormal findings on PSMA PET/CT images, [1][2][3][4] including primary lung cancer that may have intense PSMA uptake 5 and usually has intense FDG uptake, whereas benign lung neoplasms frequently show minimal FDG uptake. Pulmonary hemangioma is a rare disease that is occasionally found by diagnostic CT. 6,7 There are cases reported for abnormal PSMA uptake in vertebral, 8 liver, 9 or splenic hemangioma.…”