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Defining Brain tumor tissue using PET Ian Law, Overlæge, ph.d., dr.med. Klinik for Klinisk Fysiologi, Nuklear Medicin & PET Diagnostisk Center, Rigshospitalet Tel: 35 45 85 13 E-mail:[email protected] Ian Law, PET & Cyclotron Unit, Rigshospitalet Tumor Proton Therapy Imaging Targeting using MRI Infiltrating tumor Solid tumor Necrosis Contrast enhancing tumor MRI Problem: • Defining Tumor infiltration • 1/3 non contrast enhancing gliomas are high grade Scott, J. N., P. M. Brasher, R. J. Sevick, N. B. Rewcastle, and P. A. Forsyth (2002) Neurology 59:947-949. How often are nonenhancing supratentorial gliomas malignant? A population study. Ian Law, PET & Cyclotron Unit, Rigshospitalet [F18]-FDG is not the ideal brain tumor tracer MRI Glioblastoma Multiforme Glioblastoma Multiforme MRI & PET FDG PET Ideal Brain Tumor Tracer? • High sensitivity and specificity • Uptake in both solid and infiltrating tumor tissue • Not uptake in: • Healthy tissue • Inflammation • Epileptic activity Ian Law, PET & Cyclotron Unit, Rigshospitalet 18F-FET O-(2-[18F]flouroethyl)-L-Tyrosine BBB Tracer transport F18- FET Tyr Correlate with: - active proliferation - cell density - microvascular density - LAT1 expression - poor correlation to protein synthesis GBM L Type Amino acid transporter 1 (LAT1) Ian Law, PET & Cyclotron Unit, Rigshospitalet FET is not taken up in inflammation FDG FET HE Rau FC, Weber WA, Wester HJ et al. O-(2-[(18)F]Fluoroethyl)- L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes. Eur J Nucl Med Mol Imaging. 2002;29:1039-1046. Kaim AH, Weber B, Kurrer MO et al. (18)F-FDG and (18)F-FET uptake in experimental soft tissue infection. Eur J Nucl Med Mol Imaging. 2002;29:648-654. Ian Law, PET & Cyclotron Unit, Rigshospitalet Amino acid PET can define infiltration Infiltration Solid Kracht, L. W. et al. Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res 10, 7163-7170 (2004). Ian Law, PET & Cyclotron Unit, Rigshospitalet DD: Tumor recurrence vs. posttherapeutic changes Anaplastic astrocytoma, (WHO III) after surgery and RT MR: no recurrence 45 patients MRI No Recurrence Recurrence FET No Recurrence PET Recurrence Diffuse astrocytoma, (WHO II) after surgery and I-125 Seeds FET PET: recurrence Final pathological diagnosis No Recurrence Recurrence (N=14) (N=31) 7 7 13 1 2 29 0 31 MR: recurrence FET PET: no recurrence MRI Sensitivity Specificity 93.5 % 50 % FET PET Sensitivity Specificity 100 % 92.5 % Rachinger W et al. Neurosurgery. 2005;57:505-11 Defining a tumor: Structure vs. Function Oligoastrocytoma gr II Oligoastrocytoma gr II Malignant degeneration Wyss M, Hofer S, Bruehlmeier M et al. Early metabolic responses in temozolomide treated low-grade glioma patients. J Neurooncol. 2009;95:87-93. Ian Law, PET & Cyclotron Unit, Rigshospitalet Brain Tumor Delination Anaplastic Astrocytoma - WHO III MRI - GTV: Gross Tumor Volume: 4 ml FET PET - BTV: Biological Tumor volume: 72 ml Amino acid analogue: delineation tracer of choice Biological Tumor volume: FET Gross Tumor Volume: MR, T1+Gd Grosu, A. L. et al. Int. J. Radiat. Oncol. Biol. Phys. (2005). “In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended [greater than or equal to] 10 and 20 mm from the margin of the gadolinium enhancement. CONCLUSIONS: Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients.” Weber DC, Zilli T, Buchegger F et al. [(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for highgrade glioma. Radiat Oncol. 2008;3:44. And now for something different: Innovation diffusion Innovation Diffusion How to do it • • • Work with the culture - get legitimacy Identify opinion leaders within their group Do randomized clinical trials - Survival is the mest currency Thank you for the attention