First Clinicopathologic Evidence of a Non-PSMA-Related Uptake Mechanism for 68Ga-PSMA-11 in Salivary Glands.
The intense accumulation of prostate-specific membrane antigen (PSMA) radioligands in salivary glands is still not well understood. It is of concern for therapeutic applications of PSMA radioligands, because therapeutic radiation will damage these glands. A better understanding of the uptake mechanism is, therefore, crucial to find solutions to reduce toxicity. The aim of this study was to investigate whether the accumulation of PSMA-targeting radioligands in submandibular glands (SMGs) can be explained with PSMA expression levels using autoradiography (ARG) and immunohistochemistry (IHC). Methods: All patients gave written informed consent for further utility of the biologic material. The SMG of 9 patients, pancreatic tissue of 4 patients, and prostate cancer (PCA) lesions of 9 patients were analyzed. Tissue specimens were analyzed by means of PSMA-IHC (using an anti-PSMA-antibody and an immunoreactivity score system [IRS]) and ARG using 177Lu-PSMA-617 (with quantification of the relative signal intensity compared with a PSMA-positive standard). The SUVmax in salivary glands, pancreas, and PCA tissues were quantified in 60 clinical 68Ga-PSMA-11 PET scans for recurrent disease as well as the 9 primary tumors selected for ARG and IHC. Results: PCA tissue samples revealed a wide range of PSMA staining intensity on IHC (IRS = 70-300) as well as in ARG (1.3%-22% of standard). This variability on PCA tissue could also be observed in 68Ga-PSMA-11 PET (SUVmax, 4.4-16) with a significant correlation between ARG and SUVmax (P < 0.001, R 2 = 0.897). On IHC, ARG, and 68Ga-PSMA-11 PET, the pancreatic tissue was negative (IRS = 0, ARG = 0.1% ± 0.05%, SUVmax of 3.1 ± 1.1). The SMG tissue displayed only focal expression of PSMA limited to the intercalated ducts on IHC (IRS = 10-15) and a minimal signal on ARG (1.3% ± 0.9%). In contrast, all SMG showed a high 68Ga-PSMA-11 accumulation on PET scans (SUVmax 23.5 ± 5.2). Conclusion: Our results indicate that the high accumulation of PSMA radioligands in salivary glands does not correspond to high PSMA expression levels determined using ARG and IHC. These findings provide evidence, that the significant accumulation of PSMA radioligands in SMG is not primarily a result of PSMA-mediated uptake.
['Rupp|Niels J|NJ|', 'Umbricht|Christoph A|CA|', 'Pizzuto|Daniele A|DA|', 'Lenggenhager|Daniela|D|', 'Töpfer|Antonia|A|', 'Müller|Julian|J|', 'Muehlematter|Urs J|UJ|', 'Ferraro|Daniela A|DA|', 'Messerli|Michael|M|', 'Morand|Grégoire B|GB|', 'Huber|Gerhard F|GF|', 'Eberli|Daniel|D|', 'Schibli|Roger|R|', 'Müller|Cristina|C|', 'Burger|Irene A|IA|']
D000368:Aged D000818:Animals D000954:Antigens, Surface D001345:Autoradiography D045744:Cell Line, Tumor D004151:Dipeptides D005709:Gallium Isotopes D005710:Gallium Radioisotopes D043425:Glutamate Carboxypeptidase II D006573:Heterocyclic Compounds, 1-Ring D006801:Humans D007091:Image Processing, Computer-Assisted D007150:Immunohistochemistry D008187:Lutetium D008279:Magnetic Resonance Imaging D008562:Membrane Glycoproteins D051379:Mice D008875:Middle Aged D009368:Neoplasm Transplantation D009942:Organometallic Compounds D010179:Pancreas D049268:Positron-Emission Tomography D011446:Prospective Studies D017430:Prostate-Specific Antigen D012189:Retrospective Studies D012469:Salivary Glands D013363:Submandibular Gland
68Ga-PSMA-11 prostate-specific membrane antigen autoradiography prostate cancer 177Lu-PSMA-617 immuno-histochemistry positron emission tomography