FDG IMAGING: WHAT TECHNOLOGISTS NEED TO KNOW

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OVERVIEW OF PET
R. Edward Coleman, M.D.
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Outline of Presentation

• Description of PET
• Patient preparation / imaging
• Reimbursement
• Clinical studies oncology
• Dementia

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PET

• Molecular imaging
• Primary modality for molecular medicine
• Research / animal PET

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Positron Emitting Radionuclides

• Cyclotron Produced Generator Produced
• F-18 110 mins Ga-68 68 minsC-11 20
  mins Rb-82 76 secsN-13 10 mins
• O-15 2 mins

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Positron Annihilation
511 keV
511 keV
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Coincidence
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F-18 FDG
CH2OH
O
OH
OH
HO
18F
DGlucose
2Fluoro2DeoxyDGlucose
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FDG

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

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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

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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

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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

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Imaging

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

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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

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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

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Non-Oncologic PETMedicare Coverage

• Rb-82 myocardial perfusion
• FDG refractory seizure disorder myocardial
  viability assessment under review dementia
• N-13 ammonia myocardial perfusion

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Oncologic PETMedicare Coverage

• Diagnosis, staging and restaging
• Non-small cell lung cancer
• Colorectal cancer
• Esophageal cancer
• Head and Neck cancer
• Lymphoma
• Melanoma

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Oncologic PETMedicare Coverage

• Staging, restaging and treatment monitoring of
  breast cancer
• Thyroid cancer after therapy, TG elevated, I-131
  scan negative

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Cancers Submitted for Coverage

• Brain tumor
• Cervical cancer
• Small cell lung cancer
• Testicular cancer
• Pancreatic cancer

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Cancers Submitted for Coverage

• Ovarian cancer
• GIST
• Aggressive prostate cancer
• Multiple myeloma

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PET Scans by Type
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Clinical Indications 2002

• Lung 1024
• Lymphoma 542
• Melanoma 272
• Colorectal 244
• Breast 158
• Head Neck 83
• Esophagus 74

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Clinical Indications 2002

• Brain tumor 570
• Seizure 62
• Other 25

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Solitary Pulmonary Nodule
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FDG-PET Meta-analysis in Pulmonary Nodules

• Studies performed between 1996 and 2000
• 1474 focal pulmonary lesions
• Maximum joint sensitivity and specificity 91.2
• Sensitivity 96.8, Specificity 77.8

Gould et al JAMA 2001285914-24
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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 281336-1340

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FDG PET in Lung Cancer

• Uptake (SUV) in the primary mass correlates with
  median survival
• SUV
• SUV 10 11.4 months
• SUV 10, SPN 3 cm 5.7 month
• Ahuja et al. Cancer 1998 83918

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NSCLC - Staging
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Mediastinal Staging Meta-analysis

• Included 14 PET studies of 514 pts and 29 CT
  studies of 2226 pts
• PET Sensitivity79, Specificity91
• CT Sensitivity60, Specificity77
• Dwamena et al. Radiology 1999213503-506

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Effectiveness of PET in Preoperative Assessment
of Patients with Suspected NSCLCThe 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 (n96) 41 futile thoractomiesCWU PET
  (n92) 21 futile thoracotomiesRelative
  reduction 51 p0.003

van Tinteren et al., Lancet 2002 3591388
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The PLUS Multi-center Trial

• CWU (n96) CWU PET (n92)
• 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

van Tinteren et al., Lancet 2002 3591388
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Esophageal Cancer
Pre Therapy Post Therapy
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Villous Adenoma
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Colorectal Cancer
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Hepatic Metastases
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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 85Modality Mean
  wt sens (CI) US 55 (41, 65) CT 72 (63,
  80) MRI 76 (57, 91) PET 90 (80,
  97)

Kinkel et al Radiology 2002 24748-756
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Hodgkin Lymphoma
12/11/01
4/10/02
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Gleevec Therapy in GIST Dana-Farber Cancer
Institute
Baseline 24 hours 7 days
2 months 5.5 months
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Breast Cancer
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Change FDG-SUV Responders (n21) and
Non-Responders (n19)
With cutoff change ? 10 PPV 91 NPV 94 for
predicting response
Percent Change in SUV for FDG
Responders
Non-responders
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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

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PET/CT
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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 3 min / bed position

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Advantages of PET/CT

• Shorter scan time
• More accurate attenuation correction better
  images
• Anatomic fusion

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Small Cell Lung CA
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Integrated PET and CT in Staging Lung Cancer
(NEJM 20033482500)

• 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)

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Integrated PET and CT in Staging Lung Cancer
(NEJM 20033482500)

• 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.

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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/CT12, MRI2

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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)

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Colorectal CA
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Squamous Cell CA
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PET in Alzheimers Disease

• Request for coverage
• distinguish patients with AD from other causes
  of dementia, or assist with early diagnosis in
  patients with suspected neurodegenerative disease
  

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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

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Dementia

• Affects 8 of persons 65 years
• Affects 47 of persons 85 years
• Alzheimers disease accounts for 70

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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

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Conventional Workup of Dementia

• Lim et al (J Am Geriatr Soc 1999 47564-9)
  evaluated 134 patients with new onset of symptoms
  - diagnosis based on follow-up of 3 years.

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Conventional Workup of Dementia

• 94 AD, 40 non-AD
• Sens Spec
• Prob AD 83 55
• Prob Poss AD 85 50

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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
  1521476-1484)

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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

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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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PET

• PET assesses physiology and biochemistry, rather
  than anatomy
• Thus provides
• a different perspective on disease(characterizati
  on of biology)
• earlier, more sensitive detection of disease

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PET / CT

• Combines chemistry and anatomy
• Provides more diagnostic information than either
  modality by itself