¹⁸F-Fluorocholine PET uptake correlates with pathologic evidence of recurrent tumor after stereotactic radiosurgery for brain metastases

Purpose: Radiographic changes of brain metastases after stereotactic radiosurgery (SRS) can signify tumor recurrence and/or radiation necrosis (RN); however, standard imaging modalities cannot easily distinguish between these two entities. We investigated whether ¹⁸F-Fluorocholine uptake in surgical samples of the resected lesions correlates with pathologic evidence of recurrent tumor and PET imaging. Methods: About 14 patients previously treated with SRS that developed radiographic changes were included. All patients underwent a preoperative 40-min dynamic PET/CT concurrent with 392 ± 11 MBq bolus injection of ¹⁸F-Fluorocholine. ¹⁸F-Fluorocholine pharmacokinetics were evaluated by standardized uptake value (SUV), graphical analysis (Patlak plot; K_i ^P) and an irreversible two-compartment model (K₁, k₂, k₃, and K_i). 12 out of 14 patients were administered an additional 72 ± 14 MBq injection of ¹⁸F-Fluorocholine 95 ± 26 minutes prior to surgical resection. About 113 resected samples from 12 patients were blindly reviewed by a neuropathologist to assess the viable tumor and necrotic content, microvascular proliferation, reactive gliosis, and mono- and polymorphonuclear inflammatory infiltrates. Correlation between these metrics ¹⁸F-Fluorocholine SUV was investigated with a linear mixed model. Comparison of survival distributions of two groups of patients (population median split of PET SUV_max) was performed with the log-rank test. Results: Exactly 10 out of 12 patients for which surgical samples were acquired exhibited pathologic recurrence. Strong correlation was observed between SUV_max as measured from a surgically removed sample with highest uptake and by PET (Pearson’s r = 0.66). Patients with ¹⁸F-Fluorocholine PET SUV_max > 6 experienced poor survival. Surgical samples with viable tumor had higher ¹⁸F-fluorocholine uptake (SUV) than those without tumor (4.5 ± 3.7 and 2.6 ± 3.0; p = 0.01). ¹⁸F-fluorocholine count data from surgical samples is driven not only by the percentage viable tumor but also by the degree of inflammation and reactive gliosis (p ≤ 0.02; multivariate regression). Conclusions: ¹⁸F-Fluorocholine accumulation is increased in viable tumor; however, inflammation and gliosis may also lead to elevated uptake. Higher ¹⁸F-Fluorocholine PET uptake portends worse prognosis. Kinetic analysis of dynamic ¹⁸F-Fluorocholine PET imaging supports the adequacy of the simpler static SUV metric.