Somatostatin Receptor 2 Expression in Pituitary Neuroendocrine Tumors as a Basis for PET/MRI guided Subtype Stratification and Radiotherapy Planning

Abstract: Pituitary neuroendocrine tumors (pitNET), also known as pituitary adenomas, represent 15% of all intracranial tumors diagnosed in the United States. Postoperative MRI can underestimate residual disease extent due to postsurgical changes such as disruption of tissue planes, autologous bone and fat grafts, and free mucosal flaps. Patients with hormone-producing pitNET who are not cured with surgery may be treated medically or with radiation therapy (RT), most commonly stereotactic radiosurgery (SRS). Suppressive therapy requires lifelong administration of often-expensive medications that may have substantial off-target side effects. RT will stop the growth of residual pitNET, but only achieves long-term biochemical remission in approximately 50% of patients at 10 years. While stereotactic radiosurgery (SRS) can be more effective, MRI-based SRS that does not treat all of the residual pitNET will fail to control tumor growth and hypersecretion. PitNET express somatostatin receptor 2 (SSTR2), however the expected range of SSTR2 density and factors influencing SSTR2 expression in pitNET are not well understood. SSTR2 can be targeted with [68Ga] DOTATATE, a clinically approved PET radiotracer. Our team has pioneered a dynamic [68Ga]-DOTATATE brain PET/MRI acquisition protocol, allowing differentiation of SSTR2-positive brain and skull base neoplasms, most notably meningioma, from post-surgical and post-RT change, using SUV analysis and Patlak modeling. Given our extensive experience in clinical translation of DOTATATE PET/MRI in SSTR2-positive brain tumors, we are uniquely positioned to translate this approach in patients with pitNET. DOTATATE PET/MRI has the potential to improve diagnostic accuracy, increase our understanding of pitNET biology, and improve SRS targeting, thereby increasing local control and biochemical remission rates in pitNET. Our preliminary findings suggest that DOTATATE PET/MRI-based extent delineation, particularly of the extrasellar component, may improve radiosurgical targeting and treatment success in pitNET. However, present knowledge regarding DOTATATE PET utility in pitNET is limited. We will characterize the range of DOTATATE PET SUV in the context of clinical, demographic, and endocrine variables. We will compare PET- and MRI-guided RT planning, and evaluate the potential of PET/MRI to local control and endocrine remission rates relative to MRI-based literature benchmarks and relative to a separate MRI-based prospective institutional observational control cohort. We will determine distribution of DOTATATE PET SUV in subtotally resected pitNET, examine association with demographic variables and hormonal lineage, and compare PET/MRI- to MRI-based tumor extent delineation. We will further determine short- and intermediate-term clinical outcomes of DOTATATE PET/MRI guided SRS for residual/ recurrent pitNET. Our proposed study has the potential of improving clinical outcomes in patients with pitNET by increasing diagnostic accuracy and improving extent delineation of extrasellar disease, which will optimize radiation targeting thereby achieving greater local control and higher endocrine remission rates.