Defining Brain tumor tissue using PET

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