[18F]-Fluciclovine PET discrimination of recurrent intracranial metastatic disease from radiation necrosis

Ephraim E Parent, Dhruv Patel, Jonathon A Nye, Zhuo Li, Jeffrey J Olson, David M Schuster, Mark M Goodman, Ephraim E Parent, Dhruv Patel, Jonathon A Nye, Zhuo Li, Jeffrey J Olson, David M Schuster, Mark M Goodman

Abstract

Background: Stereotactic radiosurgery (SRS) is often the primary treatment modality for patients with intracranial metastatic disease. Despite advances in magnetic resonance imaging, including use of perfusion and diffusion sequences and molecular imaging, distinguishing radiation necrosis from progressive tumor remains a diagnostic and clinical challenge. We investigated the sensitivity and specificity of 18F-fluciclovine PET to accurately distinguish radiation necrosis from recurrent intracranial metastatic disease in patients who had previously undergone SRS.

Methods: Fluciclovine PET imaging was performed in 8 patients with a total of 15 lesions that had previously undergone SRS and had subsequent MRI and clinical features suspicious for recurrent disease. The SUVmax of each lesion and the contralateral normal brain parenchyma were summated and evaluated at four different time points (5 min, 10 min, 30 min, and 55 min). Lesions were characterized as either recurrent disease (11 of 15 lesions) or radiation necrosis (4 of 15 lesions) and confirmed with histopathological correlation (7 lesions) or through serial MRI studies (8 lesions).

Results: Time activity curve analysis found statistically greater radiotracer accumulation for all lesions, including radiation necrosis, when compared to contralateral normal brain. While the mean and median SUVmax for recurrent disease were statistically greater than those of radiation necrosis at all time points, the difference was more significant at the earlier time points (p = 0.004 at 5 min-0.025 at 55 min). Using a SUVmax threshold of ≥ 1.3, fluciclovine PET demonstrated a 100% accuracy in distinguishing recurrent disease from radiation necrosis up to 30 min after injection and an accuracy of 87% (sensitivity = 0.91, specificity = 0.75) at the last time point of 55 min. However, tumor-to-background ratios (TBRmax) were not significantly different between recurrent disease and radiation necrosis at any time point due to variable levels of fluciclovine uptake in the background brain parenchyma.

Conclusions: Fluciclovine PET may play an important role in distinguishing active intracranial metastatic lesions from radiation necrosis in patients previously treated with SRS but needs to be validated in larger studies.

Keywords: 18F-fluciclovine; Amino acid; Brain metastasis; PET; Radiation necrosis.

Conflict of interest statement

The authors have participated in sponsored research involving 18F-fluciclovine, among other radiotracers. Emory University and Dr. Mark Goodman are eligible to receive royalties for 18F-fluciclovine. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
A 54-year-old patient with metastatic renal cell carcinoma and prior stereotactic radiosurgery. Follow-up MRI demonstrated progressively enhancing brain lesions suspicious for recurrent disease. Top panel demonstrates that a right thalamic lesion (green arrow) had low fluciclovine uptake (SUVmax of 1.0) as seen on transaxial PET (a), corresponding T1 + contrast (b), focal FLAIR hyperintensity (c), and fused FLAIR and PET (d). This lesion did not increase in size on follow-up MRI and was considered consistent with radiation necrosis. A right cerebellar lesion (blue arrow) in the same patient had high fluciclovine uptake (SUVmax of 5.3) on transaxial PET (e) and corresponding T1 + contrast (f) FLAIR hyperintensity (g) and fused FLAIR and PET (h). The right cerebellar lesion was found to be recurrent metastatic disease upon resection
Fig. 2
Fig. 2
A 43-year-old patient with metastatic colon cancer with prior stereotactic radiosurgery with follow-up MRI demonstrating multiple enhancing brain lesions suspicious for recurrent disease. Top panel demonstrating a right cerebellar lesion (green arrow) with low fluciclovine uptake (SUVmax of 1.2) on transaxial PET (a) and corresponding focal FLAIR hyperintensity (b) T1 + contrast (c) and fused FLAIR and PET (d). This lesion did not increase in size on follow-up MRI and was consistent with radiation necrosis. A left occipital lesion (green arrow) in the same patient had high fluciclovine uptake (SUVmax of 2.5) on transaxial PET (e), hyperintense FLAIR (f), T1 + contrast enhancement (g), and fused FLAIR and PET (h). The left occipital lesion was found to be recurrent metastatic disease upon resection
Fig. 3
Fig. 3
Box plot diagram of SUVmax values of recurrent disease and radiation necrosis
Fig. 4
Fig. 4
Box plot diagram of TBRmax = (SUVmax tumor)/( SUVmax_normal) of recurrent disease and radiation necrosis

References

    1. Barnholtz-Sloan JS, Yu C, Sloan AE, Vengoechea J, Wang M, Dignam JJ, et al. A nomogram for individualized estimation of survival among patients with brain metastasis. Neuro Oncol. 2012;14:910–918. doi: 10.1093/neuonc/nos087.
    1. Ruzevick J, Kleinberg L, Rigamonti D. Imaging changes following stereotactic radiosurgery for metastatic intracranial tumors: differentiating pseudoprogression from tumor progression and its effect on clinical practice. Neurosurg Rev. 2014;37:193–201. doi: 10.1007/s10143-013-0504-8.
    1. Chuang M-T, Liu Y-S, Tsai Y-S, Chen Y-C, Wang C-K. Differentiating radiation-induced necrosis from recurrent brain tumor using MR perfusion and spectroscopy: a meta-analysis. PLoS ONE. 2016;11:e0141438. doi: 10.1371/journal.pone.0141438.
    1. Galldiks N, Law I, Pope WB, Arbizu J, Langen K-J. The use of amino acid PET and conventional MRI for monitoring of brain tumor therapy. NeuroImage Clin. 2017;13:386–394. doi: 10.1016/j.nicl.2016.12.020.
    1. Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med. 2001;42:1412–1417.
    1. Chao ST, Suh JH, Raja S, Lee S-Y, Barnett G. The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. Int J Cancer. 2001;96:191–197. doi: 10.1002/ijc.1016.
    1. Huang C, McConathy J. Radiolabeled amino acids for oncologic imaging. J Nucl Med. 2013;54:1007–1010. doi: 10.2967/jnumed.112.113100.
    1. Chaofeng H, Jonathan M. Fluorine-18 labeled amino acids for oncologic imaging with positron emission tomography. Curr Top Med Chem. 2013;13:871–891. doi: 10.2174/1568026611313080002.
    1. McParland BJ, Wall A, Johansson S, Sørensen J. The clinical safety, biodistribution and internal radiation dosimetry of [18F]fluciclovine in healthy adult volunteers. Eur J Nucl Med Mol Imaging. 2013;40:1256–1264. doi: 10.1007/s00259-013-2403-1.
    1. Nye JA, Schuster DM, Yu W, Camp VM, Goodman MM, Votaw JR. Biodistribution and radiation dosimetry of the synthetic nonmetabolized amino acid analogue anti-18F-FACBC in humans. J Nucl Med. 2007;48:1017–1020. doi: 10.2967/jnumed.107.040097.
    1. Terakawa Y, Tsuyuguchi N, Iwai Y, Yamanaka K, Higashiyama S, Takami T, et al. Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J Nucl Med. 2008;49:694–699. doi: 10.2967/jnumed.107.048082.
    1. Tsuyuguchi N, Sunada I, Iwai Y, Yamanaka K, Tanaka K, Takami T, et al. Methionine positron emission tomography of recurrent metastatic brain tumor and radiation necrosis after stereotactic radiosurgery: is a differential diagnosis possible? J Neurosurg. 2003;98:1056–1064. doi: 10.3171/jns.2003.98.5.1056.
    1. Lizarraga KJ, Allen-Auerbach M, Czernin J, DeSalles AAF, Yong WH, Phelps ME, et al. 18F-FDOPA PET for differentiating recurrent or progressive brain metastatic tumors from late or delayed radiation injury after radiation treatment. J Nucl Med. 2014;55:30–36. doi: 10.2967/jnumed.113.121418.
    1. Parent EE, Schuster DM. Update on 18F-Fluciclovine PET for prostate cancer imaging. J Nucl Med. 2018;59:733–739. doi: 10.2967/jnumed.117.204032.
    1. Parent EE, Benayoun M, Ibeanu I, Olson JJ, Hadjipanayis CG, Brat DJ, et al. [18F]Fluciclovine PET discrimination between high- and low-grade gliomas. EJNMMI Res. 2018;8:67. doi: 10.1186/s13550-018-0415-3.
    1. Sasajima T, Ono T, Shimada N, Doi Y, Oka S, Kanagawa M, et al. Trans-1-amino-3–18F-fluorocyclobutanecarboxylic acid (anti-18F-FACBC) is a feasible alternative to 11C-methyl-L-methionine and magnetic resonance imaging for monitoring treatment response in gliomas. Nucl Med Biol. 2013;40:808–815. doi: 10.1016/j.nucmedbio.2013.04.007.
    1. Wakabayashi T, Iuchi T, Tsuyuguchi N, Nishikawa R, Arakawa Y, Sasayama T, et al. Diagnostic performance and safety of positron emission tomography using 18F-Fluciclovine in patients with clinically suspected high- or low-grade gliomas: a multicenter phase IIb trial. Asia Ocean J Nucl Med Biol. 2017;5:10–21. doi: 10.22038/aojnmb.2016.7869.
    1. Kondo A, Ishii H, Aoki S, Suzuki M, Nagasawa H, Kubota K, et al. Phase IIa clinical study of [18F]fluciclovine: efficacy and safety of a new PET tracer for brain tumors. Ann Nucl Med. 2016;30:608–618. doi: 10.1007/s12149-016-1102-y.
    1. McConathy J, Voll RJ, Yu W, Crowe RJ, Goodman MM. Improved synthesis of anti-[18F]FACBC: improved preparation of labeling precursor and automated radiosynthesis. Appl Radiat Isot. 2003;58:657–666. doi: 10.1016/s0969-8043(03)00029-0.
    1. Miyatake S, Nonoguchi N, Furuse M, Yoritsune E, Miyata T, Kawabata S, et al. Pathophysiology, diagnosis, and treatment of radiation necrosis in the brain. Neurol Med Chir (Tokyo) 2015;55(Suppl 1):50–59. doi: 10.2176/nmc.ra.2014-0188.
    1. Weller M, van den Bent M, Tonn JC, Stupp R, Preusser M, Cohen-Jonathan-Moyal E, et al. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol. 2017;18:e315–e329. doi: 10.1016/S1470-2045(17)30194-8.
    1. Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol. 2011;29:134–141. doi: 10.1200/JCO.2010.30.1655.
    1. Hygino da Cruz LC, Jr., Rodriguez I, Domingues RC, Gasparetto EL, Sorensen AG, Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol. 2011;32:1978–1985. doi: 10.3174/ajnr.A2397.
    1. Minniti G, Clarke E, Lanzetta G, Osti MF, Trasimeni G, Bozzao A, et al. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol. 2011;6:48. doi: 10.1186/1748-717X-6-48.
    1. Barajas RF, Jr, Chang JS, Segal MR, Parsa AT, McDermott MW, Berger MS, et al. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology. 2009;253:486–496. doi: 10.1148/radiol.2532090007.
    1. Bette S, Huber T, Gempt J, Boeckh-Behrens T, Wiestler B, Kehl V, et al. Local fractional anisotropy is reduced in areas with tumor recurrence in glioblastoma. Radiology. 2017;283:499–507. doi: 10.1148/radiol.2016152832.
    1. Li H, Deng L, Bai HX, Sun J, Cao Y, Tao Y, et al. Diagnostic accuracy of amino acid and FDG-PET in differentiating brain metastasis recurrence from radionecrosis after radiotherapy: a systematic review and meta-analysis. AJNR Am J Neuroradiol. 2018;39:280–288. doi: 10.3174/ajnr.A5472.
    1. Tomura N, Kokubun M, Saginoya T, Mizuno Y, Kikuchi Y. Differentiation between treatment-induced necrosis and recurrent tumors in patients with metastatic brain tumors: comparison among 11C-methionine-PET, FDG-PET, MR permeability imaging, and MRI-ADC-preliminary results. AJNR Am J Neuroradiol. 2017;38:1520–1527. doi: 10.3174/ajnr.A5252.
    1. Yomo S, Oguchi K. Prospective study of 11C-methionine PET for distinguishing between recurrent brain metastases and radiation necrosis: limitations of diagnostic accuracy and long-term results of salvage treatment. BMC Cancer. 2017;17:713. doi: 10.1186/s12885-017-3702-x.
    1. Lohmann P, Stoffels G, Ceccon G, Rapp M, Sabel M, Filss CP, et al. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans. Eur Radiol. 2017;27:2916–2927. doi: 10.1007/s00330-016-4638-2.
    1. Ceccon G, Lohmann P, Stoffels G, Judov N, Filss CP, Rapp M, et al. Dynamic O-(2–18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy. Neuro Oncol. 2017;19:281–288. doi: 10.1093/neuonc/now149.
    1. Ulaner GA, Goldman DA, Corben A, Lyashchenko SK, Gonen M, Lewis JS, et al. Prospective clinical trial of 18F-fluciclovine PET/CT for determining the response to neoadjuvant therapy in invasive ductal and invasive lobular breast cancers. J Nucl Med. 2017;58:1037–1042. doi: 10.2967/jnumed.116.183335.
    1. Schuster DM, Nye JA, Nieh PT, Votaw JR, Halkar RK, Issa MM, et al. Initial experience with the radiotracer anti-1-amino-3-[18F]Fluorocyclobutane-1-carboxylic acid (anti-[18F]FACBC) with PET in renal carcinoma. Mol Imaging Biol. 2009;11:434–438. doi: 10.1007/s11307-009-0220-5.
    1. Oka S, Okudaira H, Ono M, Schuster DM, Goodman MM, Kawai K, et al. Differences in transport mechanisms of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid in inflammation, prostate cancer, and glioma cells: comparison with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-D-glucose. Mol Imaging Biol. 2014;16:322–329. doi: 10.1007/s11307-013-0693-0.
    1. Chernov MF, Ono Y, Abe K, Usukura M, Hayashi M, Izawa M, et al. Differentiation of tumor progression and radiation-induced effects after intracranial radiosurgery. Acta Neurochir Suppl. 2013;116:193–210. doi: 10.1007/978-3-7091-1376-9_29.

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