BIOGUIDE-X: A First-in-Human Study of the Performance of Positron Emission Tomography-Guided Radiation Therapy

Purpose: Positron emission tomography (PET) -guided radiation therapy is a novel tracked dose delivery modality that uses real-time PET to guide radiation therapy beamlets. The BIOGUIDE-X study was performed with sequential cohorts of participants to (1) identify the fl uorodeoxyglucose (FDG) dose for PET -guided therapy and (2) con fi rm that the emulated dose distribution was consistent with a physician -approved radiation therapy plan. Methods and Materials: This prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (2-5 cm) in the lung or bone. For cohort I, a modi fi ed 3 + 3 design was used to determine the FDG dose that would result in adequate signal for PET -guided therapy. For cohort II, PET imaging data were collected on the X1 system before the fi rst and last fractions among patients undergoing conventional stereotactic body radiation therapy. PET -guided therapy dose distributions were modeled on the patient ' s computed tomography anatomy using the collected PET data at each fraction as input to an " emulated delivery " and compared with the physician -approved plan. Results: Cohort I demonstrated adequate FDG activity in 6 of 6 evaluable participants (100.0%) with the fi rst injected dose level of 15 mCi FDG. In cohort II, 4 patients with lung tumors and 5 with bone tumors were enrolled, and evaluable emulated delivery data points were collected for 17 treatment fractions. Sixteen of the 17 emulated deliveries resulted in dose distributions that were accurate with respect to the approved PET -guided therapy plan. The 17th data point was just below the 95% threshold for accuracy (dose -volume histogram score = 94.6%). All emulated fl uences were physically deliverable. No toxicities were attributed to multiple FDG administrations. Conclusions: PET -guided therapy is a novel radiation therapy modality in which a radiolabeled tumor can act as its own fi du- cial for radiation therapy targeting. Emulated therapy dose distributions calculated from continuously acquired real-time PET data were accurate and machine -deliverable in tumors that were 2 to 5 cm in size with adequate FDG signal characteristics. @ 2023 Elsevier Inc. All rights reserved.