στη σταδιοποίηση του καρκίνου του προστάτη Γ. Αρσος, Γ Εργ. Πυρηνικής Ιατρικής ΑΠΘ, ΓΝΘ Παπαγεωργίου

Transcription

1 Η θέση του PET/CT στη σταδιοποίηση του καρκίνου του προστάτη Γ. Αρσος, Γ Εργ. Πυρηνικής Ιατρικής ΑΠΘ, ΓΝΘ Παπαγεωργίου

2 2014 : the Guidelines year.

3 PRINCIPLES OF IMAGING Imaging is performed for the detection and characterization of disease in order to : guide appropriate management Imaging studies should be performed based on : the best available clinical evidence and not influenced by : business or personal interests of the care provider

4 Predicting radionuclide bone scan findings in patients with newly diagnosed, untreated prostate cancer : PSA is superior to all other clinical parameters 521 randomly chosen pts mean age 70 (44 92) yrs Newly diagnosed, untreated prostate cancer Bone Scan (+) (-) PSA (ng/ml) pts with PSA 20 ng/ml : ONLY 1 Bone Scan (+) PSA<20 - NPV for Bone Scan = 99.7% Chybowski FM et al, J Urol 1991

5 <1% bone Mets! * Downstream Procedures 21% x-rays 7% CT 3% MRI Annual estimated Medicare cost (BS + downstream procedures) $11,300,000 for low/intermediate-risk pts * High-risk pts : only 62% received a BS (14% with mets) Falchook AD et al, Int J Rad Oncol 2014

6 PRE POST 10 0 Low Risk High Risk Makarov DV et al, JNCI 2013

7 challenges for radionuclide imaging diagnosis staging follow up recurrence - CRPC treatment assessment

8 Bone Scan T N M Molecular Imaging

9 PET detector CT Attenuation correction Localization : specificity

10 Production t ½ (min) 11 C Cyclotron N Cyclotron O Cyclotron F Cyclotron Ga Generator Rb Generator 1.3

11 PET radiopharmaceuticals Carbohydrate Positron emitter + Aminoacids Fatty acids Peptide Nucleotide analogues Molecular imaging!

12 FDG tumor model Normal cell Tumour cell FDG6P Glycolysis Glucose 6-phosphatase G6P Hexo kinase Glucose 6-phosphatase FDG G FDG G Glucose 6-phosphatase FDG Hexo kinase G FDG6P G6P Glucose 6-phosphatase Glycol.

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14 PET radiopharmaceuticals for Prostate Cancer Conti M, EJNMMI Phys 2014

15 DIAGNOSIS & STAGING Skeletal metastasis (M staging) is best assessed by bone scan. This may not be indicated in asymptomatic patients if the serum PSA level is <20 ng/ml in the presence of well-differentiated or moderately differentiated tumours. B In equivocal cases, 18F-fluorodeoxyglucose-PET or PET/CT could be of value, especially to differentiate active metastases and healing bones. C Heidenreich A et al Eur Urol 2014

16 CHOLINE DATA Essential component of phospholipids and cell membrane metabolism Phosphorylated by choline kinase & trapped in the cell Incorporated into cell membrane phospholipids through phosphatidylcholine synthesis Increase in malignant tumours : Cell membrane metabolism Choline use Choline Kinase expression

17 64-yrs pt3a, N0, R0, GS 7 primary PSA 1.34 ng/ml PSA 4.7 ng/ml 3 mo after RT Beheshti M, J Nucl Med 2013

18 18F-FDG PET/CT 18F-FCH PET/CT Beheshti M, Semin Nucl Med 2009

19 Krause BJ et al Urol Oncol 2013

20 Krause BJ et al Urol Oncol 2013

21 11C-Choline PET/CT DW-MRI Butiharto T et al, Eur Urol 2011

22 60 yrs GS 9 After RP + EBRT PSA 3.04 ng/ml 60 yrs After EBRT+ ADT PSA 63 ng/ml T2-MRI normal-sized Nonsuspicious iliac lymph nodes hypointense lesion in the ANT column of the right acetabulum 68Ga-PSMA PET/MRI Roethke MC et al, Eur Urol 2013

23 70-yr-old, GS 8, T1 N1) 26 months after RP PSA 2 to 7 ng/ml / 9 mo lesion 1.5 cm intense CE MRI 3.0 T : Suggestive of meningioma Schillaci O et al, NMC 2010 FP : Infections Benign Prostate Hypertrophy Other malignancies CVI : : FN : ADT

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26 Current status of choline-pet and prostate cancer Dif. benign / malignant intraprostatic T-staging of primary disease N-staging prior to primary treatment : Good specificity Low sensitivity / FN rate : PSA/PSA-kinetics Clinically : equivocal nodes / very high risk patients Positive scan > negative scan At biochemical recurrence : Promise in restaging Identifying localised dis./ excluding distant spread Treatment response assessment Radiotherapy planning no evidence increasing evidence accepted practice in UK no evidence under investigation no evidence under investigation Taylor BP et al, Trends Urol 2014

27 Glutamate carboxypeptidase II (GCPII) N-acetyl-L-aspartyl-L-glutamate peptidase I AAG peptidase prostate-specific membrane antigen (PSMA) 750 aminoacids, 84 kda Expression : prostate, kidney, small intestine, CNS Prostate : X100 of most other tissues Pro Ca : upregulation X 8-12 over noncancer prostate Higher expression : time to progression relapse Target : therapy and imaging in human prostate cancer Approved imaging agent : capromabpentide (PROSTASCINT) 2 nd -generation Abs / Low-MW ligands for imaging and therapy

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29 MoAb to the cell membrane of prostate cancer cell line LNCaP 7E11C5.3 MoAb : recognizes PSMA ProstaScint : radiolabeling of the 7E11C5.3 MoAb with indium-111 Rising PSA after brachytherapy 7 years earlier / current PSA = 1.8 ng/ml ProstaScint / CT : uptake within a small lymph node in the interaortocaval groove (arrow) Taneja SS, Rev Urol 2004

30 Afshar-Oromieh A et al, EJNMMI 2013

31 Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Pts with Biochemical Recurrence After Radical Prostatectomy Ligand : 68Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)]) 248 pts with biochemical recurrence after RP - retrospective Median PSA 1.99 ng/ml ( ) - CE-PET/CT 68Ga-PSMA PET/CT (+) in 222 (89.5%) pts > ,5-1 0,2-05 PSA ng/ml No significant difference in detection efficacy with ADT (P = ) > Φεβ <1 PSA vel ng/ml/y 61 (24.6%) pts : exclusively identified additional involved regions Eiber M et al. JNM May 1, 2015 vol. 56 no

32 PET/CT ROLE IN PROSTATE CANCER PET/CT with choline tracers may identify sites of metastatic disease in pts with biochemical recurrence after primary treatment failure Further study is needed to determine the best use of choline PET/CT imaging in pts with prostate cancer Other choline radiotracers are under evaluation Data of the utility of 18F-FDG-PET/CT in pts with prostate cancer is limited Routine use of 18F-FDG PET/CT is not recommended at this time

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34 PET/CT for prostate cancer not recommended not reimbursed not reimbursed 11C-CH 18F-FMCH 68Ga-PSMA not available 18F-FDG COST : 1458,42!!!

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