Prostate-specific Membrane Antigen Expression In Neovasculature Research Articles

Novel use of folate hydrolase 1/glutamate carboxypeptidase II (PSMA) in PET-MRI evaluation of suspected gynecologic cancers

Objective: Folate hydrolase 1/glutamate carboxypeptidase II, or prostate-specific membrane antigen (PSMA), is expressed on prostate tumor cells and on the neovasculature of nonprostate cancers. PSMA-based 18F-DCFPyL PET imaging demonstrates very high tumor-to-background ratios when studied in prostate, lung, and renal cancers. A recent immunohistochemistry (IHC) study demonstrated high PSMA expression in neovasculature of uterine and ovarian tumors, but not in normal gynecologic tissues. We hypothesized that PSMA is more highly expressed in gynecologic cancers than in normal gynecologic tissues with resultant increased 18F-DCFPyl uptake on PET imaging.

Impact of PSMA PET/CT in prostate cancer patient’s clinical management: a pictorial essay of interesting cases with histologic confirmation

Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) has a significant impact on prostate cancer (PCa) patient’s clinical management. PSMA PET/CT has changed both the paradigm of metastases spread pathway, and the PSMA specificity for detecting PCa lesions. Currently, it is accepted that PCa can spread to cervical and mediastinal lymph nodes without other intermediate lesions. PSMA expression in non-prostate cancers or benign lesions is known as well. However, information about PSMA functional specificity in clinical practice is still missing. A retrospective analysis of PSMA PET/CT studies was done to select relevant clinical cases with complete clinical history, histology results and follow-up information. Each clinical case was organized from a holistic perspective, including clinical information, 68Ga-PSMA PET/CT images, pathology results and clinical outcome. Nine clinical cases were selected to illustrate synchronous primary cancers (gastric gastrointestinal stromal tumours and clear cell renal cell carcinoma), atypical sites of PCa metastases (thyroid, liver, cervical and mediastinal lymph nodes) and some examples of PCa lung metastases with discordant PSMA findings between PET/CT examinations and immunohistochemistry. In this pictorial essay and review, the meaning of high PSMA expression in neovasculature and uncommon PCa metastatic spread were addressed. Furthermore, recent information about the possible explanation of (1) PCa metastases without PSMA expression due to dedifferentiation and specific PCa subtypes, and (2) some discordant findings on PSMA expression evaluated by PET/CT and immunohistochemistry related to the anti-PSMA antibody used in each technique is presented.

PSMA expression by microvasculature of thyroid tumors \u2013 Potential implications for PSMA theranostics

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer epithelium, making it a promising target for molecular imaging and therapy. Recently, several studies found unexpected PSMA radiotracer uptake by thyroid tumors, including radioiodine-refractory (RAIR) cancers. PSMA expression was reported in tumor-associated endothelium of various malignancies, however it has not been systematically addressed in thyroid tumors. We found that PSMA was frequently expressed in microvessels of thyroid tumors (120/267), but not in benign thyroid tissue. PSMA expression in neovasculature was highly irregular ranging from 19% in benign tumors to over 50% in thyroid cancer. Such heterogeneity was not directly attributed to endothelial cell proliferation as confirmed by immunostaining with proliferation-associated endothelial marker CD105. PSMA expression was associated with tumor size (p = 0.02) and vascular invasion in follicular carcinoma (p = 0.03), but not with other baseline histological, and clinical parameters. Significant translational implication is that RAIR tumors and high-grade cancers maintain high level of PSMA expression, and can be targeted by PSMA ligand radiopharmaceuticals. Our study predicts several pitfalls potentially associated with PSMA imaging of the thyroid, such as low expression in oncocytic tumors, absence of organ specificity, and PSMA-positivity in dendritic cells of chronic thyroiditis, which is described for the first time.

68Ga-PSMA-HBED-CC PET for Differential Diagnosis of Suggestive Lung Lesions in Patients with Prostate Cancer.

In prostate cancer (PC) patients, the differentiation between lung metastases and lesions of different origin, for example, primary lung cancer, is a common clinical question. Herein, we investigated the use of Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-HBED-CC) for this purpose. PC patients (n = 1,889) undergoing (68)Ga-PSMA PET/CT or PET/MR scans were evaluated retrospectively for suggestive lung lesions. For up to 5 lesions per patient, location, CT diameter, CT morphology, and SUVmax were determined. The standard for classification was either histopathologic evaluation or, in the case of PC metastases, responsivity to antihormone therapy. A comparison of the different classes was executed by Student t test. Prostate-specific antigen and prostate-specific membrane antigen (PSMA) immunohistochemistry were performed if histologic samples were available; (68)Ga-PSMA autoradiography was performed on an exemplary case of PET-positive lung cancer. Eighty-nine lesions in 45 patients were identified, of which 76 were classified as PC (39 proven, 37 highly probable), 7 as primary lung cancer, and 2 as activated tuberculosis; 4 lesions remained unclear. The mean SUVmax was 4.4 ± 3.9 for PC metastases and 5.6 ± 1.6 for primary lung cancer (P = 0.408). Additionally, substantial differences in SUVmax intraindividually were detected. The 2 tuberculous lesions showed an SUVmax of 7.8 and 2.5. Using immunohistochemistry, we could demonstrate PSMA expression in the neovasculature of several PSMA PET-positive lung cancers as well as in tuberculous lesions from our histologic database. Quantitative (SUV) analysis of (68)Ga-PSMA PET was not able to discriminate reliably between pulmonary metastases and primary lung cancer in PC patients. The reason for the unexpectedly high tracer uptake in non-PC lesions is not completely clear. PSMA expression in neovasculature provides a possible explanation for this finding; however, other contributing factors, such as tracer binding to proteins other than PSMA, cannot be excluded at present.