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Objective:
Intracranial metastases are one of the manifestations of advanced prostate cancer (PCa) with low detection rate on conventional imaging. There is huge a gap in the literature regarding the findings of PSMA PET/CT scans for brain lesions in these patients. As a result of that, although not clearly considered as a contraindication for radiopharmaceutical treatment, substantial caution around clinical management of patients with brain metastases exists. This study aims to characterize the PSMA PET/CT findings in correlation with brain MRI as a gold standard.

Materials and Methods:
Patients with PCa and PSMA PET/CT imaging with ¹⁸F-piflufolastat and ⁶⁸Ga-gozetotide PSMA PET/CT images of PCa patients were reviewed from August 2021 to February 2023. Patients with reported intracranial uptake were included in this study, and the site(s) and intensity of intracranial uptake were recorded. High uptake was defined as lesion SUVmax > SUVmean of liver background, and low uptake was defined as SUVmax < SUVmean of liver. The PET results were compared to brain MRI acquired within 6 months from the date of PET scan. Patients’ characteristics including age, treatment history, prostate-specific antigen (PSA) level, and neurological signs were recorded.

Results:
A total of 10/1480 (0.68%) patients (age 49-80 years) had a reported intracranial uptake on the PSMA PET/CT, with 4/10 imaged using ¹⁸F-piflufolastat and 6/10 imaged using ⁶⁸Ga-gozetotide. Of these 10 patients, 8/10 had PET imaging features suspicious for intracranial metastatic PCa, and 2/10 had features suggestive of a meningioma as confirmed on MRI. The PPV of PSMA PET for brain metastasis, which was defined as the probability that a patient with intracranial uptake had metastatic etiology, was calculated to be 80% (8/10) with MRI used as the gold standard for diagnosis. For patients with brain metastasis, 4/8 had high uptake and 4/8 had low uptake (mean SUVmax /liver SUVmean =1.2 and 0.3 respectively). For those without metastasis, 2/2 had low uptake (mean SUVmax /liver SUVmean =0.4). Most lesions (95%) had an MRI correlate. One patient had multiple subcentimeter lesions on MRI without any reported uptake on the PET. Only 2/10 patients presented with neurological symptoms. Treatment plans were changed in 5/10 patients based on the intracranial PET findings, with 3/5 having stereotactic radiosurgery, and 1/5 starting pembrolizumab for brain metastasis, and 1/5 undergoing resection of a meningioma. The PSA level was significantly higher in patients with metastasis compared to those with nonmetastatic disease (median PSA: 90.9 vs 0.15, <em>p</em> < 0.05 calculated using one-tailed Welch’s T-test).

Conclusion:
PSMA PET/CT allows for the detection of incidental intracranial lesions that may not otherwise be caught on standard of care CTs of PCa patients with PCa. Our analysis also suggests that PSA level may correlate with a higher detection rate of metastatic brain disease. PSMA PET is beneficial as an early detection tool and can guide treatment management.