Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with 18F-ML-10
Early assessment of tumor response to therapy is vital for treatment optimization for the individual cancer patient. Induction of apoptosis is an early and nearly universal effect of anticancer therapies. The purpose of this study was to assess the performance of 18F-ML-10, a novel PET radiotracer for apoptosis, as a tool for the early detection of response of brain metastases to whole-brain radiation therapy (WBRT).
Materials and methods
Ten patients with brain metastases treated with WBRT at 30 Gy in ten daily fractions were enrolled in this trial. Each patient underwent two 18F-ML-10 PET scans, one prior to the radiation therapy (baseline scan), and the second after nine or ten fractions of radiotherapy (follow-up scan). MRI was performed at 6–8 weeks following completion of the radiation therapy. Early treatment-induced changes in tumor 18F-ML-10 uptake on the PET scan were measured by voxel-based analysis, and were then evaluated by correlation analysis as predictors of the extent of later changes in tumor anatomical dimensions as seen on MRI scans 6–8 weeks after completion of therapy.
In all ten patients, all brain lesions were detected by both MRI and the 18F-ML-10 PET scan. A highly significant correlation was found between early changes on the 18F-ML-10 scan and later changes in tumor anatomical dimensions (r = 0.9).
These results support the potential of 18F-ML-10 PET as a novel tool for the early detection of response of brain metastases to WBRT.
KeywordsPositron emission tomography Response assessment Whole-brain radiation therapy Brain metastases Apoptosis
- 3.Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363(9422):1665–72.PubMedCrossRefGoogle Scholar
- 19.Galban CJ, Chenevert TL, Meyer CR, Tsien C, Lawrence TS, Hamstra DA, et al. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. Clin Cancer Res. 2011;17(14):4751–60.PubMedCrossRefGoogle Scholar
- 22.Moffat BA, Chenevert TL, Lawrence TS, Meyer CR, Johnson TD, Dong Q, et al. Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. Proc Natl Acad Sci U S A. 2005;102(15):5524–9.Google Scholar
- 24.Hoebers FJ, Kartachova M, de Bois J, van den Brekel MW, van Tinteren H, van Herk M, et al. 99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy. Eur J Nucl Med Mol Imaging. 2008;35(3):509–18.PubMedCrossRefGoogle Scholar
- 27.Zhou D, Chu W, Chen DL, Wang Q, Reichert DE, Rothfuss J, et al. [18F]- and [11C]-labeled N-benzyl-isatin sulfonamide analogues as PET tracers for apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging study of apoptosis in Fas-treated mice using [11C]WC-98. Org Biomol Chem. 2009;7(7):1337–48.PubMedCrossRefGoogle Scholar
- 29.Hentschel M, Appold S, Schreiber A, Abolmaali N, Abramyuk A, Dorr W, et al. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer. Eur J Nucl Med Mol Imaging. 2011;38(7):1203–11.PubMedCrossRefGoogle Scholar