The Role of [(68)Ga]Ga-DOTA-SSTR PET Radiotracers in Brain Tumors: A Systematic Review of the Literature and Ongoing Clinical Trials

SIMPLE SUMMARY: [(68)Ga]Ga-DOTA-SSTR PET imaging has recently been introduced in the management of patients with brain tumors, mostly meningiomas and pituitary adenomas or carcinomas. The current literature demonstrated the superior diagnostic accuracy of this imaging modality, especially for lesions difficult to be detected or characterized on conventional imaging protocols, such as skull base or transosseous meningiomas. [(68)Ga]Ga-DOTA-SSTR PET tracers also seem to provide superior volume contouring for radiotherapy planning and may also be used to evaluate the tumor’s overexpression of somatostatin receptors for devising patient-tailored peptide receptor radionuclide therapy. In this review, we comprehensively analyzed the current literature discussing the implementation of [(68)Ga]Ga-DOTA-SSTR PET imaging in brain tumors, further presenting ongoing clinical trials and suggesting potential future applications. ABSTRACT: Background: The development of [(68)Ga]Ga-DOTA-SSTR PET tracers has garnered interest in neuro-oncology, to increase accuracy in diagnostic, radiation planning, and neurotheranostics protocols. We systematically reviewed the literature on the current uses of [(68)Ga]Ga-DOTA-SSTR PET in brain tumors. Methods: PubMed, Scopus, Web of Science, and Cochrane were searched in accordance with the PRISMA guidelines to include published studies and ongoing trials utilizing [(68)Ga]Ga-DOTA-SSTR PET in patients with brain tumors. Results: We included 63 published studies comprising 1030 patients with 1277 lesions, and 4 ongoing trials. [(68)Ga]Ga-DOTA-SSTR PET was mostly used for diagnostic purposes (62.5%), followed by treatment planning (32.7%), and neurotheranostics (4.8%). Most lesions were meningiomas (93.6%), followed by pituitary adenomas (2.8%), and the DOTATOC tracer (53.2%) was used more frequently than DOTATATE (39.1%) and DOTANOC (5.7%), except for diagnostic purposes (DOTATATE 51.1%). [(68)Ga]Ga-DOTA-SSTR PET studies were mostly required to confirm the diagnosis of meningiomas (owing to their high SSTR2 expression and tracer uptake) or evaluate their extent of bone invasion, and improve volume contouring for better radiotherapy planning. Some studies reported the uncommon occurrence of SSTR2-positive brain pathology challenging the diagnostic accuracy of [(68)Ga]Ga-DOTA-SSTR PET for meningiomas. Pre-treatment assessment of tracer uptake rates has been used to confirm patient eligibility (high somatostatin receptor-2 expression) for peptide receptor radionuclide therapy (PRRT) (i.e., neurotheranostics) for recurrent meningiomas and pituitary carcinomas. Conclusion: [(68)Ga]Ga-DOTA-SSTR PET studies may revolutionize the routine neuro-oncology practice, especially in meningiomas, by improving diagnostic accuracy, delineation of radiotherapy targets, and patient eligibility for radionuclide therapies.