Rationale for a trial of ¹⁸F-fluciclovine PET/MR-guided radiation therapy for glioblastoma

Glioblastoma (GBM) is the most common primary malignant brain tumor. Newly-diagnosed glioblastoma management includes maximum safe resection followed by radiotherapy with concurrent temozolomide and the maintenance temozolomide for 6-12 cycles. This postoperative chemoradiotherapy approach has resulted in a significant increase in median PFS (5.0 vs. 6.9 months) and OS (12.1 vs. 14.6 months) compared to radiotherapy alone[1]. However, despite such multi-modality therapy, the median survival for GBM remains poor at approximately 15-16 months in contemporary series[2,3]. Although adjuvant chemoradiotherapy has been shown to increase survival, a predominant pattern of failure remains local[6,7]. Part of the challenge is that the radiation therapy target is difficult to define as it solely relies on anatomic imaging and its variants. Anatomic imaging is inherently limited in its ability to inform about the underlying biology, whether of the tumor or surrounding tissue. We set out to overcome the limitations of conventional MRI-guided radiation therapy by leveraging and repurposing a synthetic amino acid positron emission tomography (PET) radiotracer, trans-1-amino-3-¹⁸F-fluorocyclobutanecarboxylic acid (anti-FACBC or ¹8F-fluciclovine) that specifically targets the over-expression of amino acid transporters found in many cancers, including gliomas. ¹⁸F-fluciclovine is a ¹⁸F-labeled amino acid PET tracer that has already received FDA approval for imaging prostate cancer. (author)