A pilot study to assess the status of PSMA as a theranostic target in recurrent glioblastoma multiforme

Glioblastoma multiforme (GBM), a tumor derived from glial cells, is the most common primary brain tumor in adults accounting for 45.2% of malignant primary brain and CNS tumors. Primary GBMs account for 80% of GBMs and mostly occur in older patients with a mean age of 62 years while secondary GBMs occur from lowergrade astrocytoma or oligodendroglioma mostly in younger patients with a mean age of 45 years. GBM is a highly vascularized tumor. The World Health Organization in their 2021 classification defines GBM as a grade IV cancer characterized as malignant, mitotically active, and predisposed to necrosis associated with a very poor prognosis with a mean age of survival of approximately six months that can be very difficult to cure, and the current treatment options have no optimal outcomes. As the treatment options in recurrent high-grade gliomas are limited, new therapeutic perspectives with the use of radiolabeled agents are studied.

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein, expressed predominantly in prostate cancer (PCa) cells. It is encoded by the FOLH1 gene located on the short arm of the chromosome. It has neuropeptidase and folate hydrolase activity and plays a role in cell survival, cell migration, and nutrient uptake. The internalization process of the PSMA receptor allows for the bound molecules to reach significant concentration within the cell and this process can be imaged using a radioactive tracer tagged with Gallium 68. Apart from expression in PCa cells, it was found to have PSMA expression in the neovasculature of triplenegative breast cancer, lung cancer, pancreatic cancers, and certain other malignancies.

177Lutetium (177Lu), with a half-life of 6.73 days when combined with PSMA ligands (such as PSMA 617) can be used for the destruction of tumor cells due to its medium‐energy β‐emission (497 keV) and a mean tissue penetration of 670 μm. It also emits low‐energy γ‐rays at 208 and 113 keV with 10 and 6% abundance respectively which allows for its imaging via gamma camera.

There is proven efficacy of 177Lutetium (177Lu) therapy in Prostate cancer (mCRPC) (10) and a couple of studies have tried to study the efficacy in GBM with encouraging results. Hence, the purpose of this study is to determine the status of PSMA as a theranostic target using 68Ga PSMA-11 and 177Lu-PSMA-617 in GBM patient.