New imaging techniques: let there be light. Felix M. Mottaghy Department of Nuclear Medicine University Hospital KU Leuven

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1 New imaging techniques: let there be light Felix M. Mottaghy Department of Nuclear Medicine University Hospital KU Leuven

2 Medical imaging and the pathology cascade Molecular/Cellular disturbance Alterations in physiology Diagnostic approach : Nuclear/Molecular Medicine Radiology Structural lesion

3 Improvement of hardware

4 SPECT PET Hybrid imaging CT

5

6 SPECT of the heart

7 Combined SPECT/CT

8 Courtesy of dr. E. D Hondt, Kortrijk Remnant ablation with I131 in a patient with thyroid cancer Conventional planar post therapy scan

9 Anatomic localisation with SPECT/CT Courtesy of dr. E. D Hondt, Kortrijk Remnant ablation with I131 in a patient with thyroid cancer

10 Patient with pain in the right tibia Courtesy of dr. E. D Hondt, Kortrijk

11 SPECT/CT of the same patient Courtesy of prof. dr. A. Maes, Kortrijk

12 PET CT

13 Advantages of PET/CT Cohade et al., 2003

14 Czernin et al., 2007

15 1 + 1 = 3?

16 software

17 Molecular interactions of radiolabeled probes In vivo imaging of biological processes with radiolabeled molecular probes Radiometall α-, β - - Strahler Receptor Enzyme Transporter Mechanism of localization Visualization of overexpression or increased activity of: Receptors Enzymes Transporters

18 Generator Cyclotron 99 Mo 99m Tc 18 F, 11 C, 15 O, 13 N

19 FDG FDG Glukose Glukose- Transporter FDG Glukose Hexokinase Glukose-6- Phosphatase Hexokinase Glukose-6- Phosphatase FDG-6-PO 4 Glukose-6-PO 4 Glykolyse Glykolyse

20 Beyond FDG in oncology... tumour metabolism [ 18 F] FDG > glucose metabolism [ 18 F] FLT > DNA synthesis (proliferation) [ 11 C] Methionine > protein synthesis [ 18 F] FET > protein synthesis [ 11 C] Choline > membrane synthesis [ 11 C] Acetate > lipid synthesis tumour environment [ 15 O] Water > tumour perfusion [ 18 F] MISO > hypoxia tumour characteristics [ 99m Tc]-His-Annexin > apoptosis [ 123 I]-Hypericin > necrosis [ 68 Ga] DOTATOC > somatostatin receptor expression

21 Choline and cancer Choline = precursor for lipid layer of cell membrane Increased uptake of choline in cancer cells higher proliferation rate upregulation of Choline kinase Phosphaditylcholine In vivo- imaging of Choline metabolism MR spectroscopy PET

22 Clincial applications of Choline Prostate carcinoma primary staging local recurrence

23 Thymidylate synthesis DNA dttp 5`- FU dtdp De-novopathway dump Thymidylate synthetase N 3,N 10 -methylene tetrahydrofolate dtmp Thymidine kinase 1 tetrahydrofolate dihydrofolate Dihydrofolate reductase es MTX Thymidine es ei es: equilibrative transporter nbmpr sensitive ei: equilibrative transporter nbmpr insensitive es FLT Ara-C Salvagepathway

24 A. FDG B. FDG C. FLT D. FLT Early response evalutation with FDG and FLT-PET/CT in a patient with refractory Mantle cell lymphoma treated with the mtor inhibitor temsirolimus A. FDG-PET/CT before therapy shows a focal uptake in the left costodiafragmatic sinus B. FDG-PET/CT after 6 weeks of therapy with temsirolimus shows persistent FDG-uptake in this lesion C. FLT-PET/CT before therapy confirms the same lesion in the left costodiafragmatic sinus D. FLT-PET/CT exactly 7 days after the first administration of temsirolimus shows complete disappearance of all FLT uptake The patient obtained a disease free status after a few months of therapy and is still in complete remission after a follow-up of 27 months

25 Amino-Acids aminoacid transporter increased in tumors L-carrier mostly used in brain tumours

26 Glioblastoma multiforme MRI T1 MRI T2 CT PET C-11 Methionin PET/CT

27 18 F-FET can differentiate tumour grade by kinetic analysis Popperl et al. J Nucl Med 2006; Weckesser et al, Eur J Nucl Med Molec Imag 2005 Differentiatie low-high grade met sens/spec 92% (n=45)

28 Somatostatinanaloga: Physiological mechanism SSR N SS I N SS C N SS C C SS: Somatostatinanaloga SSR: Somatostatinreceptor I: Internalisation : Radionuclide Nucleus

29 Somatostatinreceptorscintigraphy Octreoscan In-111 Octreotid

30 Somatostatinreceptorexpression in NET [ 111 In]Octreotid SSR-Szintigraphie [ 68 Ga]DOTATOC PET SCLC with neuroendocrine properties

31 [ 68 Ga] DOTATOC PET/CT in an eye lesion suspect for recurrent carcinoid tumour FDG DOTATOC cc FDG a b DOTATOC d Van Riet et al., in press e f

32 Annexin V 36 kda protein with high affinity for phosphatidylserin (1) Annexin V stains apoptotic cells in vitro (2) 1. Martin SJ et al., Exp Med Koopman et al., Blood 1994

33 Imaging apoptosis 99m Tc-(CO) 3 -HIS-cysAnx 1h p.i. µspect imaging EUROPACT project: Maastricht, Aachen, Leuven Baseline low liver uptake Transverse Sagittal Coronal 90 after anti-fas (hepatic apoptosis) High liver uptake

34 Triple Tracer Imaging Perfusion Apoptosis Necrosis

35 [ 13 N]NH 3 ANT LV LAT INF [ 123 I]MIH [ 99m Tc]Annexin [ 13 N]NH 3 Apex INF LV ANT [ 123 I]MIH Base [ 99m Tc]Annexin [ 13 N]NH 3 Base LV Apex [ 123 I]MIH [ 99m Tc]Annexin

36 Conclusion Integrated anatomic and functional or metabolic imaging improves diagnostic accuracy Development of specific tracers improves diagnostic specificity

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