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Molecular imaging
- 2. Molecular imaging offers unique insights into the human body that enable physicians to personalize patient care. In terms of diagnosis, molecular imaging is able to: provide information that is unattainable with other imaging technologies or that would require more invasive procedures such as biopsy or surgery identify disease in its earliest stages and determine the exact location of a tumor, often before symptoms occur or abnormalities can be detected with other diagnostic tests SNMI
- 4. SYNTHESIS OF THE PET TRACERS
- 5. BIOLOGICAL MARKER (PET PROBE) 18F- + (labelling radiopharmaceitical agent) FDG
- 7. BIOMARKERS
- 12. PET TRACERS PET PROBE BIOMARKER USE 18 F 18 F- FDG GLUCOSE METABOLISM Lymphoma Head & Neck ca NSCLC, melanoma, colon ca, Cardiac Viability 18-F-FET AMINO ACID METABOLISM CANCER (BRAIN- glioma) 18 F- FLT TISSUE PROLIFERATION CANCER (BRAIN) 18-F- FMISO/FAZA TISSUE HYPOXIA CANCER (GIST/SARCOMA) 18-F- FCH STEROL PROLIFERATION CANCER (Prostate) 68 Ga 68-Ga- Octreotate TUMOUR RECEPTOR OVEREXPRESSION CANCER (NET) 82-Rb ( PERFUSION) Myocardial Perfusion
- 13. 18-F- FDG (glucose metabolism) 58-year0old man –staging of NSCLC
- 14. Semiquatitative marker: SUV – = tracer activity / injected dose normalized to body weight. • SUV was a significant and independent predictor of local control and disease-free survival . Tatsuo Torizuka et al AJR 2009; 192:W156-W160
- 15. Tumour FDG roles SUVmax (FDG) Published study Colorectal metastasis Prognostic marker 10.0 Christopher C.R. et al.J Nuc Med 2007 - (5) Non-small lung carcinoma Predictor for recurrent tumour 4.5 Shiono et al. J. of Thoracic Oncology.2011- (6) Thymic tumour Predictor for malignancy 8.5 Reimer SE et al. J Nucl Med (1998)- (7) Thymoma Predictor for tumour aggressiveness 10.0 Yon et al. J Nucl Med (2006) - (8) Liposarcoma Predictor for disease - free survival 3.6 Winfried B. et al. European Journal of Nuclear Medicine and Molecular Imaging. 2006- (23) Invasive ductal breast cancer Predictor for progression-free disease survival 6.6 Bong-Il S et al. Nucl Med Mol Imaging. (2011) – (32) Phaechromocytoma/ Paraganglioma recurrence Predictor for tumour aggressiveness 9.1 Fathinul F et al (unpublished) –(39)
- 16. UTILITY OF FDG -PET AS A BIOMARKER • LOCALISATION • PRE-TREATMENT STAGING • TREATMENT MONITORING • PREDICTION OF TUMOUR RECURRENCE/AGGRESSIVENESS • PROGNOSTIC FACTOR
- 17. LYMPHOMA
- 18. FDG-PET ( treatment monitoring) B-cell lymphoma (pre versus post treatment)
- 19. Experience of FDG-PETCT in GIT (esophageal tumour) n= 18 referral for tumour restaging
- 22. POTENTIAL ROLE OF FDG_PET-CT IN NEUROENDOCRINE TUMOUR
- 23. The critical need for Surrogate Biomarker •Relative rare, NET cause substantial morbidity in community •Symptoms are innocuous •Survival is long, suffering can be protracted •Slow growth , low response rates using concentional treatment •Use of the structural imaging : Detection of secondary deposits are poor •NET: clonal heterogeneity- discrimination of benign from malignant is difficult on histology •WHO: malignant disease is solely based on the basis of metastasis/retrospective analysis
- 24. Introduction •>13 known neuroendocrine cells that can undergo malignant transformation [Rindi G, Kloppel G. Endocrine tumors of the gut and pancreas tumor biology and classification. Neuroendocrinology 2004; 80(Suppl 1): 1215] •Hormonal excess to constituitional symptoms •Peptide hormones bind to stimulatory or inhibitory cell surface receptors (SSTR) •NET express SSTR (subtype 2) S 2
- 25. NEUROENDOCRINE TUMOUR • BIOLOGICAL PROPERTIES Malignant NET constitutes a rare heterogenous group of tumour NET adrenal, endocrine Islets (thyroid , pancreas) Digestive and respiratoyr tracts Indolent Growth • Well differentiated aggressive • Poorly differentiated Malignant potential • De- differentiated
- 26. 600 × 411 - ... progression to a higher grade of de- differentiation and malignancy FDG-PET: Prediction of aggressiveness
- 27. Imaging Biomarkers! In this patient with metastatic NET, co-registered image in transaxial planes demonstrate sites (cross- hairs) of high FDG uptake on PET (left panels) lacking in somatostatin receptor expression based on In-111 octreotide SPECT (right panels) scanning. ….unlike most tumours, no molecular or cellular markers can identify a PCC/PGL as malignant. Vascular invasion and cellular atypia, do not definitively identify a PCC/PGL as malignant
- 28. PET with 68Ga DOTA- Octreotide
- 29. FDG-PET : Tumour Localisation • ? Reliability of FDG-PET – : useful marker in localising metastatic/recurrent PCC/PGL Timmers HJ, et al. Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. J.Clin.Oncol. 2007 Jun 1;25(16):2262-2269
- 31. Mean SUVmax between local control & metastasis SUVmax: 7.78 SUVmax: 14.08
- 32. Factor No of Patients p Local control (n=9) Metastasis (n=14) Tumour SUVmax <9.2 >9.2 9 0 6 8 **0.03 Tumour size <2.0cm >2.0cm 9 0 9 5 0.14 Serum catecholamine positive negative 2 7 12 2 0.18 Predictors for localcontrol/metastasis ** : Fischer’s exact test : significant value P<0.05
- 33. •The problem with molecular heterogeneity •Tumour with indistinguishable histology demonstrated quite different response to therapy FDG-PET: Pre-treatment staging:
- 35. Targeted Therapy R.J. Hicks. Cancer Imaging. 2010; 10(1A): S83–S91.
- 36. Biomarkers In vitro tumour signaling Glut-1 Glycolytic metabolism Ki-67 Tumour proliferation p 53 Tumour apoptosis CORELATION WITH PRECLINICAL BIOMARKERS
- 37. After 6mo
- 39. Thank you
- 40. After 6mo FDG; Disease predictor