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 F-18-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 F-18-Fluorocholine. F-18-Fluorocholine pharmacokinetics were evaluated by standardized uptake value (SUV), graphical analysis (Patlak plot; K-i(P)) and an irreversible two-compartment model (K-1, k(2), k(3), and K-i). 12 out of 14 patients were administered an additional 72 +/- 14 MBq injection of F-18-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 F-18-Fluorocholine SUV was investigated with a linear mixed model. Comparison of survival distributions of two groups of patients (population median split of PET SUVmax) 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 SUVmax as measured from a surgically removed sample with highest uptake and by PET (Pearson's r = 0.66). Patients with F-18-Fluorocholine PET SUVmax > 6 experienced poor survival. Surgical samples with viable tumor had higher F-18-fluorocholine uptake (SUV) than those without tumor (4.5 +/- 3.7 and 2.6 +/- 3.0; p = 0.01). F-18-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 F-18-Fluorocholine accumulation is increased in viable tumor; however, inflammation and gliosis may also lead to elevated uptake. Higher F-18-Fluorocholine PET uptake portends worse prognosis. Kinetic analysis of dynamic F-18-Fluorocholine PET imaging supports the adequacy of the simpler static SUV metric.