Milan Grkovski1, Zachary A Kohutek2,3, Heiko Schöder4,5, Cameron W Brennan6,7, Viviane S Tabar6, Philip H Gutin6, Zhigang Zhang8, Robert J Young3, Bradley J Beattie1, Pat B Zanzonico1, Jason T Huse7,9,10, Marc K Rosenblum10, Ronald G Blasberg3,11,12, John L Humm1, Kathryn Beal13. 1. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 2. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 3. Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. 4. Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 5. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 6. Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 7. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 8. Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 9. Pathology Department, MD Anderson Cancer Center, Houston, TX, USA. 10. Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 11. Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 12. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. 13. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. bealk@mskcc.org.
Abstract
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; KiP) and an irreversible two-compartment model (K1, k2, k3, and Ki). 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 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 18F-Fluorocholine PET SUVmax > 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.
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; KiP) and an irreversible two-compartment model (K1, k2, k3, and Ki). 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 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 18F-Fluorocholine PET SUVmax > 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.
Authors: Milan Grkovski; Karem Gharzeddine; Peter Sawan; Heiko Schöder; Laure Michaud; Wolfgang A Weber; John L Humm Journal: J Nucl Med Date: 2018-04-06 Impact factor: 10.057
Authors: Laura M Kenny; Kaiyumars B Contractor; Rainer Hinz; Justin Stebbing; Carlo Palmieri; Jie Jiang; Sami Shousha; Adil Al-Nahhas; R Charles Coombes; Eric O Aboagye Journal: Clin Cancer Res Date: 2010-08-03 Impact factor: 12.531
Authors: Eija Sutinen; Martti Nurmi; Anne Roivainen; Matti Varpula; Tuula Tolvanen; Pertti Lehikoinen; Heikki Minn Journal: Eur J Nucl Med Mol Imaging Date: 2003-11-20 Impact factor: 9.236
Authors: Joshua D Schaefferkoetter; Ziting Wang; Mary C Stephenson; Sharmili Roy; Maurizio Conti; Lars Eriksson; David W Townsend; Thomas Thamboo; Edmund Chiong Journal: EJNMMI Res Date: 2017-03-21 Impact factor: 3.138
Authors: Timothy J Kaufmann; Marion Smits; Jerrold Boxerman; Raymond Huang; Daniel P Barboriak; Michael Weller; Caroline Chung; Christina Tsien; Paul D Brown; Lalitha Shankar; Evanthia Galanis; Elizabeth Gerstner; Martin J van den Bent; Terry C Burns; Ian F Parney; Gavin Dunn; Priscilla K Brastianos; Nancy U Lin; Patrick Y Wen; Benjamin M Ellingson Journal: Neuro Oncol Date: 2020-06-09 Impact factor: 12.300
Authors: Catherine Coolens; Matt N Gwilliam; Paula Alcaide-Leon; Isabella Maria de Freitas Faria; Fabio Ynoe de Moraes Journal: Cancers (Basel) Date: 2021-05-23 Impact factor: 6.639
Authors: William C Newman; Jacob Goldberg; Sergio W Guadix; Samantha Brown; Anne S Reiner; Katherine Panageas; Kathryn Beal; Cameron W Brennan; Viviane Tabar; Robert J Young; Nelson S Moss Journal: J Neurooncol Date: 2021-06-19 Impact factor: 4.506