What to Trust, PSA or [68Ga]Ga-PSMA-11: Learn from Experience

Rita Viglialoro,1,2,* Enrica Esposito,1,2,* Roberta Zanca,1,2 Marco Gessi,3 Tommaso Depalo,1,2 Gayane Aghakhanyan,1,2 Francesco Bartoli,1,2 Martina Sollini,4,5 Paola Anna Erba1,2,6 1Regional Center of Nuclear Medicine, Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy; 2Azienda Ospedaliero Universitaria Pisana, Pisa, Italy; 3Neuropathology Unit, Division of Pathology Fondazione Policlinico Universitario “A.Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 4Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090, Italy; 5IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 6Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Centre, University Medical Center Groningen, Groningen, the Netherlands*These authors contributed equally to this workCorrespondence: Paola Anna ErbaDepartment of Translational Research and New Technology in Medicine, via Savi 10, Pisa, 56126, ItalyTel +39-050-992115Fax +39-050-992124Email p.erba@unipi.itAbstract: Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient’s management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [68Ga]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [68Ga]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition – from the vertex to thigh – should be always considered, regardless of the PSA level.Keywords: [68Ga]Ga-PSMA-11 PET/CT, biochemical recurrence, brain metastases, multimodal imaging, prostate cancer, PSA