© 2019 The Author(s) Purpose: The aim of this study was to report the treatment planning feasibility of dose escalation to suspicious lymph nodes (LNs) for a series of men who underwent pretreatment [18F]fluciclovine positron emission tomography (PET)/magnetic resonance imaging (MRI). Methods and Materials: Cases of men with prostate cancer who enrolled in a clinical trial of pretreatment [18F]fluciclovine PET who had suspicious LNs were selected. Pelvic LNs <1 cm were defined as positive based on [18F]fluciclovine-PET if their maximum standardized uptake value (SUVmax) was ≥1.3-fold greater than the reference blood pool SUVmean, and LNs ≥1 cm were defined as positive if the SUV was greater than the reference SUV bone marrow reference. For each case, a radiation treatment plan was generated to deliver 70 Gy to the prostate and proximal seminal vesicles, 60.2 Gy to the PET-positive LNs, and 50.4 Gy to the elective nodal regions, simultaneously in 28 fractions of 2.5 Gy, 2.15 Gy, and 1.8 Gy, respectively. Treatment planning goals were defined a priori. The resulting target volume and organ-at-risk dosimetry were compared with the original treatment plan. Results: Four cases were identified, with between 1 and 5 [18F]fluciclovine PET–positive LNs each. Goals for the prostate and elective nodal target volumes were successfully met in all cases. The goal of covering more than 90% of the positive LN planning target volume by the prescription dose of 60.2 Gy was met in 3 of the 4 cases. This goal was not met in 1 case, but 100% of clinical target volume was covered by 60.2 Gy. The primary organ-at-risk tradeoff was that a small volume (0.5-8.2 cm3) of small bowel would receive ≥54 Gy in each case. Conclusions: These preliminary results suggest that [18F]fluciclovine PET/MRI directed dose escalation of suspicious pelvic LNs is likely feasible in the setting of definitive radiation therapy. The potential clinical benefit of dose escalating [18F]fluciclovine PET–positive LNs should be investigated in a prospective clinical trial.