Advances in oncological PET/CT Imaging

3,976 views

Published on

the advances in PET/CT imaging in oncology

Published in: Health & Medicine

Advances in oncological PET/CT Imaging

  1. 1. Dr. Hussein Farghaly, MDDr. Hussein Farghaly, MD Assistant professor and ConsultantAssistant professor and Consultant nuclear Medicinenuclear Medicine Advances in oncological PETAdvances in oncological PET ImagingImaging
  2. 2. Outline  Introduction  Limitations of PET/CT imaging  Advances of PET/CT Imaging: New PET radiotracer PET/CT protocols Soft Wear Enhance the specificity Insturmentation PET/MRI PEM
  3. 3. IntroductionIntroduction  FDG PET/CT has emerged as a powerful imaging tool for the detection of various cancers.FDG PET/CT has emerged as a powerful imaging tool for the detection of various cancers. The combined acquisition of PET and CT has synergistic advantages over PET or CT aloneThe combined acquisition of PET and CT has synergistic advantages over PET or CT alone and minimizes their individual limitations.and minimizes their individual limitations.  It is a valuable tool for staging and restaging of some tumors and has an important role in theIt is a valuable tool for staging and restaging of some tumors and has an important role in the detection of recurrence in asymptomatic patients with rising tumor marker levels and patientsdetection of recurrence in asymptomatic patients with rising tumor marker levels and patients with negative or equivocal findings on conventional imaging techniques. It also allows forwith negative or equivocal findings on conventional imaging techniques. It also allows for monitoring response to therapy and permitting timely modification of therapeutic regimens. Inmonitoring response to therapy and permitting timely modification of therapeutic regimens. In about one third of the patients, the course of management is changedabout one third of the patients, the course of management is changed
  4. 4. Clinical Impact of PET/CT Advantages of PET/CT over Conventional anatomical imaging: • Characterizing lesions difficult to biopsy • Detecting occult cancer • Determining extent of cancer and response to therapy Significant clinical impact  More accurate diagnosis  Avoidance of unnecessary tests, and (potentially) harmful procedures  Better treatment or management (PET - CT changes management in about one third of cancer patient) Is FDG PET/CT a completely perfect test?
  5. 5. Limitations in FDG – PET/CTLimitations in FDG – PET/CT imagingimaging Due to FDG:Due to FDG: False positiveFalse positive False negativeFalse negative Radiation exposure from radiotracer (8Radiation exposure from radiotracer (8 mSv)mSv) Due to instrumentation:Due to instrumentation: mis-registration (motion artifact)mis-registration (motion artifact) low spatial resolutionlow spatial resolution Radiation exposure from CT (7 -25 mSv)Radiation exposure from CT (7 -25 mSv) Long study timeLong study time
  6. 6. Limitations in FDG – PET/CTLimitations in FDG – PET/CT imagingimaging  False positive:False positive:  ““Normal” uptakeNormal” uptake (head & neck, muscle, brown fat, GI/GU uptake)(head & neck, muscle, brown fat, GI/GU uptake)  false-positive FDG uptake can occur in PET/CT in relation tofalse-positive FDG uptake can occur in PET/CT in relation to granulomatous disease or inflammation. Some benign tumors, such asgranulomatous disease or inflammation. Some benign tumors, such as colonic adenomas and fibroids, may also demonstrate intense FDG uptakecolonic adenomas and fibroids, may also demonstrate intense FDG uptake  False negative:False negative:  Small lesions (partial volume loss)Small lesions (partial volume loss)  Hypometabolic lesions (low grade tumor, well differentiated NET,Hypometabolic lesions (low grade tumor, well differentiated NET, mucinous secreting tumor, RCC, some low grade lymphoma likemucinous secreting tumor, RCC, some low grade lymphoma like small lymphocytic lymphoma, peripheral T-cell lymphomasmall lymphocytic lymphoma, peripheral T-cell lymphoma  Elevated serum glucoseElevated serum glucose
  7. 7. RADIOCHEMISTRY INSTRUMENTATION HW/SW ADVANCES IN PET IMAGING NEW SCINTILLATION CRYSTALS Dose reduction soft wear PET/MRI PEM NEW TRACERS PET
  8. 8. Advances in PETAdvances in PET RadiotracerRadiotracer
  9. 9.  Glucose metabolism [Glucose metabolism [1818 F]FDGF]FDG  Protein synthesis C-11-methionine  Membrane function [Membrane function [1111 C]CholineC]Choline  ProliferationProliferation [[1818 F]FLTF]FLT  HypoxiaHypoxia [[1818 F]FMISOF]FMISO [18F]FAZA[18F]FAZA [64Cu]ATSM[64Cu]ATSM  ApoptosisApoptosis [[1818 F]Annexin VF]Annexin V  AngiogenesisAngiogenesis [[1818 F]NGR-peptideF]NGR-peptide  Neuroendocrine tumorsNeuroendocrine tumors [[110110 In]OctreotateIn]Octreotate [68Ga] DOTATOC[68Ga] DOTATOC TRACERS for TUMOR CHARACTERIZATIONTRACERS for TUMOR CHARACTERIZATION Advances in PET RadiotracerAdvances in PET Radiotracer
  10. 10. Normal distribution of FDG and C-11 Methionine C-11-methionineC-11-methionine Benjamin et al; 2010 Anticancer Ther. 10(5), 609–613 (2010) Posterior fossa glioma.
  11. 11. C-11-methionineC-11-methionine (A) 18F-FDG; (B) contrast-enhanced MRI; (C) 11C-MET PET. Glioblastoma in the right frontal lobe, which is hard to delineate in the 18F-FDG PET. However, amino-acid PET with 11C-MET clearly shows the lesion with excellent tumor to background contrast. Benjamin et al; 2010 Anticancer Ther. 10(5), 609–613 (2010) A B C
  12. 12. left frontal grade II fibrillary astrocytoma (post-left frontal grade II fibrillary astrocytoma (post- surgery and post-radiotherapy)surgery and post-radiotherapy) C-11-methionineC-11-methionine Benjamin et al; 2010 Anticancer Ther. 10(5), 609–613 (2010)
  13. 13. 11C-choline11C-choline Richter et al;, Mol Imaging Biol (2009)
  14. 14. 11C-choline11C-choline Fifty-five-year-old patient with increasing PSA level (1.43 μg/l), 27 months after radical prostatectomy (Gleason score8). Coronal (left), axial (middle), and sagittal (right) fused image projections of PET/CT scans. Focal 11C-choline uptake (a) in right (bold arrow) and left (thin arrow) iliac region revealed lymph node involvement, not observed with 18F-FDG PET (b). Richter et al;, Mol Imaging Biol (2009)
  15. 15. Pure BronchioloalveolarPure Bronchioloalveolar CarcinomaCarcinomaCT [11 C]Choline PET [18 F]FDG PET SUV = 1.73 Picchio et al; current radiopharmaceutical, 2011
  16. 16. Dehdashti et al., Eur J Nucl Med Mol Imaging (2010 5 32:344–350 11C-Acetate11C-Acetate
  17. 17. Chitneni et al,; J Nucl Med 2011; 52:165–168 18F-misonidazole (FMISO) PET scans in RT Planning HYPOXIA IMAGING  [[1818 F]FMISOF]FMISO 18F-misonidazole [18F]FAZA[18F]FAZA 18F-fluoroazomycinarabinofuranoside [64Cu]ATSM[64Cu]ATSM 64Cu-diacetylbis ( N4-methylthiosemicarbazone)
  18. 18. Adapted from MacManus et al, Radiotherapy and Oncology 2013 PET/CT in Radiation Therapy planning
  19. 19. GEMINI TFGEMINI TF PET/CT scanner withPET/CT scanner with TruFlight technologyTruFlight technology
  20. 20. Outline  PET/CT principle  Indeterminate lung nodules  Lung cancer Staging and Restaging of known tumor Monitoring therapy Early detection of tumour recurrence Impact on radiation therapy planning
  21. 21. Indeterminate lung nodules  Accounts for ≈ 20% of newly diagnosed lung cancer  CXR and CT: not accurate to differentiate benign from malignant non-calcified pulmonary nodules that are between 1-3 cm in diameter  Initial presentation in 20% - 30% of lung cancer  Morphologic stability over 2 years: reliable sign of benignity:  Doubling time of malignant nodules: 30-400 days  Doubling in volume results in 26% increase in diameter
  22. 22. Visual Analysis:Visual Analysis: nodule activity vs mediastinal blood pool activinodule activity vs mediastinal blood pool activi Quantitative analysis: SUV (standardized uptake value)Quantitative analysis: SUV (standardized uptake value) [[1818 F]FDG PETF]FDG PET Measure of metabolic activity of SPNMeasure of metabolic activity of SPN SUV = 7.3 CT [18 F]FDG PET A SPN with SUV more than 2.5 is considered to be malignant
  23. 23. PIOPILN Study Prospective investigation of PET in lung nodules  90 patients from 5 centers with indeterminate nodules (CT)  Size range: 0.7 to 4 cm  All nodules had histology: 67% were malignant  PIOPLIN and other studies: SUV > 2.5 = visual (FDG uptake > mediastinal blood pool) Sensitivity: 90-100% Specificity: 69-95%  False positive: Active granuloma  False negative: Bronchioalveolar, mucinous carcinoma, carcinoid Hyperglycemia (decreases uptake by up to 50%)  Lowe VJ et al. J Clin Oncol 1998;16:1075-1084.  Nomori H et al. Lung cancer 2004;45:19-27.  Herder GJ et al. Eur J Nucl Med Mol Imag 2004;31:1231-1236.  Lowe VJ et al. J Nucl Med 1994;35:1771-1776.  Nomori H et al. Ann Thorac Surg 2005;79:984-988.
  24. 24. Diagnostic Accuracy of FDG PET and CT for the Characterization of Lung Nodule  344 patients for which definite diagnosis was obtained  Prevalence of malignancy: 53%  Average size: 16 mm PETPET CTCT Sensitivity 91.7% 95.6% Specificity 82.3% 40.6% Fletcher JW et al. J Nucl Med 2008;49 (2):179- 185
  25. 25. Middle-aged woman with a 1.5 cm lung nodule SUV is 6.2
  26. 26. Question What should be done next?  A. Follow-up  B. Biopsy  C. Chemotherapy  D. Antibiotics
  27. 27. Question What should be done next?  A. Follow-up  B. Biopsy  C. Chemotherapy  D. Antibiotics
  28. 28. Middle-aged patient with a 1.4 cm lung nodule SUV is 1.2
  29. 29. Question What should be done next?  A. Biopsy  B. Reassure the patient that the nodule is benign  C. Follow-up with CT at 3-6 months interval for 2 years  D. Follow-up with chest X-ray in 6 months
  30. 30. Question What should be done next?  A. Biopsy  B. Reassure the patient that the nodule is benign  C. Follow-up with CT at 3-6 months interval for 2 years  D. Follow-up with chest X-ray in 6 months
  31. 31. ACCP Evidenced-Based Clinical Practice Guidelines: Recommendation for FDG PET  PET recommended: Probability of cancer low to moderate (5%-60%) and an indeterminate nodule measures at least 8-10 mm.  PET NOT recommended: SPN that has a high probability of malignancy (>60%) or nodule < 8-10 mm
  32. 32. Staging NSCLC T staging: tumor size  T1 < 3 cm  T2 > 3 cm  T3 > 3 cm with chest wall, pleural, or pericardial extension  T4 with invasion of adjacent organs N staging: nodal metastases  N0: no nodes  N1: ipsilateral hilar nodes  N2: ipsilateral mediastinal or subcarinal nodes  N3: contralateral nodes or scalene/supraclavicular nodes M Staging: distant metastases  M0: no distant metastases  M1: distant metastases present
  33. 33. FDG PET for Staging T staging: The extent of the primary tumor determines therapeutic management. Imaging is done to assess the size of the tumor and the extent of pleural, chest wall or mediastinal invasion. CT and MRI are useful for confirming gross chest wall and mediastinal invasion. But they are inaccurate in differentiation between anatomic contiguity and subtle invasion. FDG PET alone: limited for T staging due to poor anatomic resolution, lack of anatomical landmark. PET/CT: improve staging by clearly demarcating the actual extent of the tumor and involvement of chest wall, diaphragm, mediastinal pleura or pericardium or main bronchus (T3 staging). Padma; et al, 2011.
  34. 34. T staging cont.:  similarly, it is useful to determine the involvement of mediastinal, vertebral and vital structures, such as the great vessels, trachea, esophagus or heart (T4 staging).  Also it is used to evaluate additional pulmonary nodules in the same lobe/ipsilateral lung having primary lung cancer, and determine the likelihood of malignancy in these nodules.  CT is rarely able to differentiate between reactive and malignant pleural effusion whereas malignant pleural effusion showed FDG uptake in PET (stage M1a).  It also has a role in guiding biopsy in patient with disease recurrence.
  35. 35. 66 year-old with right hilar mass Primary lung ca with atelectasis
  36. 36. Lung cancer staging scan with incidental second primary Coleman et al; 2006
  37. 37. N staging: •The precise characterization of mediastinal lymph nodes is crucial for determining nodal (N) stage and thus resectability in patients with NSCLC. •CT and MRI: limited by size criteria. • FDG PET: best to detect tumor in normal size lymph nodes
  38. 38. CTCT  Depending on size criteria on CT a lymph node with a short-axis diameter greater than 1 cm is considered enlarged and a predictor for metastasis. However, this method has proven inaccurate. In one study, 44% of metastatic lymph nodes in patients with NSCLC measured less than 1 cm, and 77% of patients without metastatic lymph nodes had a lymph node measuring greater than 1 cm in the short-axis diameter.  Several meta-analyses have reported low sensitivities and specificities of CT in the assessment of mediastinal lymph-node involvement, ranging from 50% to 65% and from 65% to 85%, respectively. Prenzel et al; 2003.
  39. 39. FDG PET/CTFDG PET/CT  Depending on the metabolic activity within the lymph node FDG PET can characterize mediastinal LN.  PET positive mediastinal findings should be histologically or cytologically confirmed due the fact that FDG is also taken by inflammatory process.  In patients with negative mediastinal PET images invasive staging can be omitted and it is estimated that the introduction of PET has reduced the number of mediastinoscopies by 65%  Also in case of central tumors, PET hilar N1 disease, low FDG uptake of the primary tumour, invasive staging with mediastinoscopy remains indicated.
  40. 40. Performance of different locoregional staging techniques (adapted from Toloza 2003).
  41. 41. Staging PET/CT in 74-year-old woman with 2.6-cm left lower lobe SCCStaging PET/CT in 74-year-old woman with 2.6-cm left lower lobe SCC Diagnostic axial contrast-enhanced CT scan shows multiple small subcentimeter lymph nodes scattered throughout mediastinum, primarily in lower left paratracheal region. Fused axial PET/CT image shows uptake in lower left paratracheal lymph nodes and 3- mm lower right paratracheal lymph node With metastatic involvement, confirmed at mediastinoscopy. Given presence of contralateral lymph node metastases, patient received chemotherapy and radiation instead of surgical
  42. 42. Initial staging PET/CT for 56-year-old man with 1.8-cm adenocarcinoma in right upper lobe and long history of sarcoidosis Axial contrast-enhanced CT scan shows 1.8-cm right upper lobe nodule with extensive mediastinal and hilar lymphadenopathy Fused axial PET/CT image confirms intense uptake in right upper lobe nodule and lymph nodes. Lymph node biopsies performed during mediastinoscopy showed only granulomatous inflammation from sarcoidosis and no evidence of tumor Given this finding, patient was sent for curative resection
  43. 43. M Staging:  Common metastases to adrenals, skeleton, liver, brain.  FDG PET is superior to conventional imaging: Detect metastases > ~7 mm when CT and MRI are normal or equivocal Detect unsuspected distant metastases: ~13% of patients Stage I: 7.5% Stage II: 18% Stage III: 24%  Change management: 18% of cases Peterman RM et al N Engl J Med 2000;343:254-261 Baum RP et al. Q J Nucl Med 2004;48:119-142.
  44. 44. PET/CT for the Characterization of Adrenal Masses in Patients with lung Cancer Giles et al; AJR:192, April 2009
  45. 45. Bury T et al. Eur J Nucl Med 1998;25:1244-1247.
  46. 46. TubercolosisTubercolosis SarcoidosisSarcoidosis AspergillosisAspergillosis HistoplasmosisHistoplasmosis CryptococcosisCryptococcosis False-positive results:False-positive results: Inflammatory lesions (mainly granulomas) Limitations of FDG-PET for LungLimitations of FDG-PET for Lung Nodule Characterization and NSCLC:Nodule Characterization and NSCLC:
  47. 47. maxSUV: 2.6 48 year-old female with a pulmonary mass 48 year-old female with a pulmonary mass
  48. 48. Histological TypeHistological Type CarcinoidCarcinoid Pure Bronchioloalveolar Car (BAC),Pure Bronchioloalveolar Car (BAC), mucinous camucinous ca neuroendocrine tumorneuroendocrine tumor Well differentiated typeWell differentiated type Lesion Dimension:Lesion Dimension: Small lesion < 6-8 mmSmall lesion < 6-8 mm % of viable neoplastic% of viable neoplastic cells in SPNcells in SPN Limitations of FDG-PET for Lung NoduleLimitations of FDG-PET for Lung Nodule Characterization and NSCLC:Characterization and NSCLC: False-negative resultsFalse-negative results HyperglycemiaHyperglycemia:: > 200 mg/dl = PET not performed> 200 mg/dl = PET not performed
  49. 49. [18 F]FDG PETCT Fused Lung nodule 4 mm in diameter ?
  50. 50. [18F]FDG PETCT CT- PET SPN: 4 mm in diameter
  51. 51. 52 years woman with an infiltrative lung nodule maxSUV: 1.9
  52. 52. Question What is the differential diagnosis?  A. Neuroendocrine tumor  B. Bronchioalveolar carcinoma  C. Infection  D. All of the above
  53. 53. Question What is in the differential diagnosis?  A. Neuroendocrine tumor  Bronchioalveolar carcinoma  C. Infection  D. All of the above
  54. 54. New Techniques to overcome LimitationsNew Techniques to overcome Limitations of FDG-PET in NSCLCof FDG-PET in NSCLC  Imprecise physiologic and anatomic registration, most common adjacent to the diaphragm and heart, can lead to misregistration artifact. (RESPIRATORY GATING)  Many processes with increased metabolic activity, such as infection and inflammation, show increased uptake on PET. (DUAL TIME POINT TECHNIQUE)  Tumor with low FDG uptake (Carcinoid,Carcinoid, BAC, mucinous ca, neuroendocrine tumor, Well differentiated type) OTHER PET RADIOTRACER.
  55. 55. Pure BronchioloalveolarPure Bronchioloalveolar CarcinomaCarcinomaCT [11 C]Choline PET [18 F]FDG PET SUV = 1.73
  56. 56. Dual-Time-Point F-18 FDG PET/CT E SUV 5.7 D SUV 7.1 PET/CT imaging was performed 60 and 120 minutes after injection
  57. 57.  Seth Kligerman1 and Subba Digumarthy: Staging of Non–Small Cell Lung Cancer Using Integrated PET/CT. AJR 2009; 193:1203–1211.  Dominique Delbeke: Role of FDG PET and PET/CT Imaging in Indeterminate Pulmonary Nodules and Lung CancerCongreso Chileno de Medicina Nuclear, Santiago, Chile 13-14 Noviembre 2008.  Padma S, Shanmuuga P. and Shamily G.: Role of PET in carcinoma lung evaluation:. Journal of cancer rearach and therapeutics-April-June 2011-Volume 7-Issue 2.  Didier Lardinois: Pre- and intra-operative mediastinal staging in non-small-cell lung cancer. Swiss Med Wkly. 2011;141:w13168.  Kiyoshi Shibuya, Kenzo Hiroshima and Takehiko Fujisawa: Comparison of Endobronchial Ultrasound, Positron Emission Tomography, and CT for Lymph Node Staging of Lung Cancer. Chest 2006;130;710-718  Khaled Alkhawaldeh,, Hans-J Biersack,, Anna Henke,, and Samer Ezziddin: Impact of Dual-Time- Point F-18 FDG PET/CT in the Assessment of Pleural Effusion in Patients With Non– Small-Cell Lung Cancer. Clin Nucl Med 2011;36: 423–428) ReferencesReferences
  58. 58. Why PET-CT?Why PET-CT? THANK YOU

×