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OVERVIEW OF PET

Outline of Presentation. Description of PETPatient preparation / imagingReimbursementClinical studies

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OVERVIEW OF PET

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    3. PET Molecular imaging Primary modality for molecular medicine Research / animal PET

    4. Positron Emitting Radionuclides Cyclotron Produced Generator Produced F-18 : 110 mins Ga-68 : 68 mins C-11 : 20 mins Rb-82 : 76 secs N-13 : 10 mins O-15 : 2 mins

    5. Positron Annihilation

    8. F-18 FDG

    9. FDG F-18 (cyclotron produced) has 110 min half-life FDG readily available commercially at most sites Synthesis units make large quantities reproducibly

    10. FDG Competes with serum glucose for accumulation After phosphorylated, metabolically trapped except in liver where it is dephosphorylated Tumors have increased concentrations of glucose transporter proteins and/or hexokinase enzymes

    11. Patient Preparation Goal is to have low serum glucose and insulin levels Should be without caloric intake (encourage to drink water) for 4 hrs Can take medications Obtain routine serum glucose

    12. Imaging Minimum time delay from FDG administration Brain - 30 min Whole-body - 45 min Brain imaging 1 min acquisition for positioning 3D acquisition for 8 mins calculated attenuation correction

    13. Imaging Whole body imaging 5-7 bed positions 4 min. emission, 2.5 min. transmission per bed position

    14. PET Reimbursement Complex, evolving process Dependent on FDA approval of drugs Facilitated by FDAMA (1997) Reimbursable indications Determined by technology assessment panels of third party payers Process dominated by CMS

    15. Medicare Reimbursement Hospitals paid under HOPPS/APC rules Reimbursement for others set by local carrier G codes used for billing instead of CPT codes Effective April 2002, APC technical payment for whole-body PET set at $1850 (including FDG) Professional reimbursement remains at ~ $80 vs. ~ $186 for CT of chest, abdomen, pelvis vs. ~ $165 for gated myocardial SPECT

    16. Non-Oncologic PET Medicare Coverage Rb-82: myocardial perfusion FDG: refractory seizure disorder myocardial viability assessment under review: dementia N-13 ammonia: myocardial perfusion

    17. Oncologic PET Medicare Coverage Diagnosis, staging and restaging Non-small cell lung cancer Colorectal cancer Esophageal cancer Head and Neck cancer Lymphoma Melanoma

    18. Oncologic PET Medicare Coverage Staging, restaging and treatment monitoring of breast cancer Thyroid cancer after therapy, TG elevated, I-131 scan negative

    19. Cancers Submitted for Coverage Brain tumor Cervical cancer Small cell lung cancer Testicular cancer Pancreatic cancer

    20. Ovarian cancer GIST Aggressive prostate cancer Multiple myeloma Cancers Submitted for Coverage

    22. Clinical Indications: 2002 Lung 1024 Lymphoma 542 Melanoma 272 Colorectal 244 Breast 158 Head & Neck 83 Esophagus 74

    23. Clinical Indications: 2002 Brain tumor 570 Seizure 62 Other 25

    24. rachelrachel

    25. FDG-PET: Meta-analysis in Pulmonary Nodules

    26. FDG-PET as a Metabolic Biopsy 63 lung lesions - biopsy “unsuccessful” or “too dangerous” PPV = 90%; NPV = 100% (visual analysis) False positive results: 2 with mycobacteria infection, 3 resolved over 12 months Hain et al. Eur J Nucl Med 2001; 28:1336-1340

    27. FDG PET in Lung Cancer Uptake (SUV) in the primary mass correlates with median survival SUV < 10 24.6 months SUV > 10 11.4 months SUV > 10, SPN > 3 cm 5.7 month Ahuja et al. Cancer 1998; 83:918

    28. Brown-mcbrid Brown-mcbrid

    29. Mediastinal Staging: Meta-analysis Included 14 PET studies of 514 pts and 29 CT studies of 2226 pts PET Sensitivity=79%, Specificity=91% CT Sensitivity=60%, Specificity=77% Dwamena et al. Radiology 1999;213:503-506

    30. Effectiveness of PET in Preoperative Assessment of Patients with Suspected NSCLC The PLUS Multi-center Trial 188 patients with NSCLC randomized to conventional work-up (CWU) ? PET Endpoint: futile thoracotomy benign disease exploratory thoracotomy only IIIA (N2) or IIIB disease relapse or death within 12 months CWU (n=96): 41% futile thoractomies CWU + PET (n=92): 21% futile thoracotomies Relative reduction: 51%; p=0.003

    31. The PLUS Multi-center Trial CWU (n=96) CWU + PET (n=92) No thoracotomy 18 (19%) 32 (35%) Confirmed N2/N3 10 18 Confirmed distant metastases 1 7 Benign primary lesion 2 3 Other tumor 2 1 Intercurrent disease/refused 3 3 Non-futile thoracotomy 39 (41%) 41 (44%) Futile thoracotomy 39 (41%) 19 (21%) Benign 7 2 Exploratory thoracotomy 1 1 IIIA (N2) 6 4 IIIB 6 2 Recurrence/death < 1 yr 19 10

    32. Bracey 11/01 - 02/02Bracey 11/01 - 02/02

    34. Loftus Loftus

    36. Detection of Hepatic Metastases from Cancers of the GI Tract: Meta-Analysis Used 111 data sets: 9 US, 25 CT, 11 MRI, 9 PET At a specificity higher than 85% Modality Mean wt sens (CI) US 55 (41, 65) CT 72 (63, 80) MRI 76 (57, 91) PET 90 (80, 97)

    37. Boso Boso

    39. Foster Foster

    41. Improving the Performance of PET Scanners Accelerating pace of technical innovation New scintillation crystals Lutetium oxyorthosilicate (LSO) [Lu2SiO5(Ce)] Gadolinium oxyorthosilicate (GSO) [Gd2SiO5(Ce)] Higher light output and shorter decay time than BGO Improved NEC = reduced scanning time New BGO detector design More sensitive Faster patient throughput

    42. PET/CT

    43. PET / CT Patient dosing of FDG 140 uCi / kg (10 – 20 mCi) Patient imaging Scout view obtained CT from external auditory meatus to prox thigh PET scan acquisition <150 lbs 2 min / bed position >150 lbs 3 min / bed position

    44. Advantages of PET/CT Shorter scan time More accurate attenuation correction – better images Anatomic fusion

    48. Integrated PET and CT in Staging Lung Cancer (NEJM 2003;348:2500) Prospective study of 50 patients with proven or suspected NSCLC Evaluated PET and CT alone, visually correlated PET and CT, and integrated PET-CT for TNM staging Histology: adeno ca (28), SCC (13), large cell (8), MALT (1-excluded)

    49. Integrated PET and CT in Staging Lung Cancer (NEJM 2003;348:2500) PET/CT provided additional information in 20/49 patients Exact location of lymph nodes (9) Precise evaluation of chest wall (3) and mediastinal (3) invasion Differentiation between tumor and inflammation (7) Exact location of distant metastases (2) PET/ CT significantly more accurate than others for tumor staging and than PET for nodal staging.

    50. Wholebody PET/CT and MRI for Tumor Staging (Antoch, Essen, Submitted) Studied 98 patients with various malignancies. PET/CT correctly TNM staged 75/98 (77%) pts. MRI correctly TNM staged 53/98 (54%) pts. Impact on patient management: PET/CT=12, MRI=2

    51. Wholebody PET/CT and MRI for Tumor Staging (Antoch, Essen, Submitted) Accuracy PET/CT MRI T stage 34/46 (80%)* 24/46 (52%) N stage 91/98 (93%)* 77/98 (79%) M stage 92/98 (94%)* 91/98 (93%)

    55. PET in Alzheimer’s Disease Request for coverage … distinguish patients with AD from other causes of dementia, or assist with early diagnosis in patients with suspected neurodegenerative disease …

    56. Criteria for PET in Dementia Progressive decline in cognitive domain and/or cognitive impairment (change from baseline) present for at least 6 months Not suffering from severe dementia Making a diagnosis will impact care

    57. Dementia Affects 8 % of persons > 65 years Affects 47 % of persons > 85 years Alzheimer’s disease accounts for 70 %

    58. Rationale for Early Diagnosis of AD Cholinesterase inhibitors delay decline in memory and cognitive function (9-12 months) and need for institutionalization (18 months) Better planning for future - delays nursing home placement an average of 11 months

    59. Conventional Workup of Dementia Lim et al: (J Am Geriatr Soc 1999; 47:564-9) evaluated 134 patients with new onset of symptoms - diagnosis based on follow-up of 3 years.

    60. Conventional Workup of Dementia 94 AD, 40 non-AD Sens Spec Prob AD 83 55 Prob + Poss AD 85 50

    61. Anatomic Imaging in Dementia CT and/or MRI detects unsuspected lesions (strokes and tumors) in approximately 5% of patients In a 7 center study, less than 30% of patients diagnosed as vascular dementia actually had isolated cerebrovascular disease and 55% had AD on pathological diagnosis (Am J Psychiatr 1995; 152:1476-1484)

    62. PET in Dementia Pattern of decreased FDG in AD in parietotemporal cortex sparing basal ganglia, thalamus, cerebellum, brainstem and cortical regions mediating sensory and motor functions. Extent of hypometabolism correlates with severity of cognitive impairment May be unilateral early, more symmetric as disease progresses

    63. MitchellMitchell

    64. PricePrice

    65. TaylorTaylor

    67. PET and Neuropathologic Correlation Study N Sens Spec Hoffman (J Nucl Med) 22 88% 67% Multicenter study (JAMA) 138 94% 73%

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