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

Abstract

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. Methods: PC patients (n 5 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 SUV max 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. Results: 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 SUV max was 4.4 ± 3.9 for PC metastases and 5.6 ± 1.6 for primary lung cancer (P 5 0.408). Additionally, substantial differences in SUV max intraindividually were detected. The 2 tuberculous lesions showed an SUV max 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. Conclusion: 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.

PSMA expression by microvasculature of thyroid tumors – Potential implications for PSMA theranostics

“…Immunohistochemical studies reported PSMA expression in non-neoplastic regenerative tissue, ganglionic cells, and microvessels of tuberculosis lesions 34–36 . Here, we describe for the first time frequent PSMA expression in dendritic cells of lymphoid follicles in Hashimoto’s thyroiditis and cervical lymph nodes.…”

PSMA Ligands for PET Imaging of Prostate Cancer

“…Accordingly, there is increasing evidence that PSMA ligand uptake is not exclusively specific for PC. A large number of case series and reports describe increased PET signal in benign lesions (e.g., neurogenic tissue, Paget disease, thyroid adenoma, granulomatous disease, and adrenal adenoma) as well as in malignant diseases (e.g., renal cell carcinoma, lung cancer, glioblastoma, hepatocellular carcinoma, and thyroid cancer) (87)(88)(89)(90)(91)(92)(93)(94)(95). Supplemental Table 1 (supplemental materials are available at http://jnm.snmjournals.org) summarizes the current evidence in the literature.…”

PSMA Theranostics Using PET and Subsequent Radioguided Surgery in Recurrent Prostate Cancer

“…It has to be noted, however, that several reports have also described PSMA-avid lesions not related to PCa, and these differential diagnoses have to be considered when evaluating PSMA-based examinations. [12][13][14][15][16][17][18][19][20][21][22][23] However, current available clinical and preclinical studies show high image contrast and specificity, exemplarily demonstrated by this case, explaining the current fast distribution of PSMA-PET for the evaluation of PCa.…”