NEW DEVELOPMENTS IN IMAGING IN MEDICINE SYMPOSIUM OF THE LATIN AMERICAN SECTION AMERICAN NUCLEAR SOCIETY

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NEW DEVELOPMENTS IN IMAGING IN
MEDICINESYMPOSIUM OF THE LATIN AMERICAN
SECTIONAMERICAN NUCLEAR SOCIETY

Rio de Janeiro June 13 16, 2005

• PET/CT
• A New Standard for Oncologic
• Imaging in Brazil
• Edwaldo E. Camargo, M.D.
• Nuclear Medicine Division
• Sirio-Libanes Hospital
• Sao Paulo, Brazil

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PET/CT in Brazil a New Standard

• Current Dilemma
• Insufficient 18F-FDG
• to justify PET/CT scanners
• vs
• Abundant positron emitters (baby cyclotrons)

• State Monopoly
• vs
• Free Enterprise

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PET/CT in Brazil a New Standard

• Cyclotrons Available Today
• IEN, Rio de Janeiro (1978) 24 MeV
• IPEN, Sao Paulo (1979) 24 MeV
• IPEN, Sao Paulo (1998) 30 MeV
• IEN, Rio de Janeiro (2003) 11 MeV

• Possible Additional Cyclotrons
• Recife ? MeV
• Belo Horizonte ? MeV
• Goiania ? MeV
• Porto Alegre ? MeV
• Curitiba ? MeV

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PET/CT in Brazil a New Standard

• PET/CTs and PETs Available Today
• Sao Paulo
• 3 PET/CTs
• 1 PET
• Rio de Janeiro
• 1 PET/CT
• 1 PET

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PET/CT in Brazil a New Standard

• Positron Emitters Production
• 18F-FDG, from IPEN, Sao Paulo
• (4 days/week)
• 18F-FDG, from IEN, Rio de Janeiro
• (? days/week)
• Other Emitters?
• carbon-11 (20 minutes)
• nitrogen-13 (10 minutes)
• oxygen-15 (02 minutes)

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PET/CT in Brazil a New Standard

• 18F-FDG Distribution
• Sao Paulo
• Rio de Janeiro
• Campinas
• Other cities Brasília?

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Rio de Janeiro
375 km
90 km
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Recife
Goiânia

• Campinas

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PET/CT in Brazil a New Standard

• TUMOR VIABILITY
• I-131 or I-123 IODIDE
• GALLIUM-67
• THALIUM-201
• Tc-99m SESTAMIBI I-131 or I-123
  MIBG In-111 OCTREOTIDE
• MONOCLONAL ANTIBODIES

F-18 FDG

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PET/CT in Brazil a New Standard

• IT IS NOT POSSIBLE TO PRACTICE CLINICAL
  ONCOLOGY WITHOUT 18F-FDG
• Abass Alavi, M.D.
• Director, Nuclear Medicine Division
• University of Pennsylvania, Philadelphia, USA
• Jornada Paulista de Radiologia, São Paulo, 2002

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PET/CT in Brazil a New Standard

• 18F-FDG, a glucose analog, a tracer of glucose
  metabolism that is trapped in the cell after
  conversion to 18F-FDG6-PO4 by hexokinase.
• Tissues with high levels of glucose-6-phosphatas
  e such as the liver, kidneys and intestines
  accumulate 18F-FDG6-PO4 to a lesser extent.

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GLUCOSE METABOLIC PATHWAYS
PET/CT in Brazil a New Standard
hexokinase
Glucose glucose glucose-6-phosphate
glucose-6-phosphatase
hexokinase
X
18F-FDG 18F-FDG
18F-FDG-6-phosphate
glucose-6-phosphatase
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BABYCYCLOTRON
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PET/CT in Brazil a New Standard

• Positron Emitters
• Radionuclides T ½
• Oxygen-15 2 minutes
• Nitrogen-13 10 minutes
• Carbon-11 20 minutes
• Fluorine-18 110 minutes
• Iodine-124 4.2 days

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PRINCIPLE OF POSITRON EMISSION TOMOGRAPHY
? 511 keV
Positron emitter
?
180
?- electron
? 511 keV
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PET / CTSCANNER
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PET/CT Configuration

• CT up front
• PET moves backwards for maintenance
• Single tunnel

CT
PET
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BIOGRAPH PET/CT

• PET 
• Detectors BGO
• Crystals per detector block 64
• Number of detector blocks 288
• Number of BGO crystals 18,432
• Transaxial resolution (NEMA
  2001) FWHM _at_ 1 cm 4.5 mm               
   
• FWHM _at_ 10 cm 5.6 mm
• Axial resolution (NEMA 2001) FWHM _at_ 0 cm
  4.2 mm                  FWHM _at_ 10 cm
  5.7 mm 
• CT 
• Scanning time 80 s standard
• Rotation 0.8 1.0 and 1.5 s
• Slice width 1, 2, 3, 5, 8 and 10 mm
• Minimum slice width 1 mm
• High contrast resolution 0.32 and 0.36 mm 

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NORMAL
JACO 10/03/2004
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PET/CT in Brazil a New Standard

• PET/CT
• STANDARD UPTAKE VALUE (SUV)
• Mean ROI Activity mCi/ml
• SUV
• Injected Dose mCi / Body Weight g

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PET IN CLINICAL ONCOLOGY

• Types of Tumors
• Brain
• Head and Neck
• Lung
• Colorectal, Esophagus, Stomach
• Breast, Uterus, Ovary

• Malignant Melanoma
• Lymphoma
• Neuroblastoma
• Kidney, Prostate, Bladder, Seminoma
• Other

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PET/CT in Brazil a New Standard
Since May 30, 2003, we have imaged over 2,200
patients with this approximate distribution
Oncology 97.0 Neurology 2.5
Cardiology 0.4
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PET/CT in Brazil a New Standard
In Oncology, there is the following approximate
distribution G-I tract 29 Gynecological
tumors 16 Lung 12 Lymphomas
9 Malignant melanoma 6 G-U tumors
5 Head and neck tumors 3 Other
(includes check-ups) 17.
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PET/CT in Management Change
RESTAGING AND MANAGEMENT CHANGE
UPSTAGING DOWNSTAGING
MANAGEMENT CHANGE
M. MELANOMA 43 21 64
COLORECTAL 25 25 50
NON-HODGKIN 22 27 50
HODGKIN 25 16 41 BREAST 14 14
28 PROSTATE 9 0 9
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PET/CT in Management Change
ADVANTAGES OF PET/CT OVER PET

• PET/CT precisely identifies, localizes and
  delineates size and extent of a lesion
• gtgt essential data for surgical and
  radiation therapy planning
• Goerres GW et al. J Nucl Med 2004 45 66S-71S
  

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PET/CT in Management Change
ACB, 17 y.o. female Hx Medullary thyroid
carcinoma (MEN 2B disease) after total
thyroidectomy. Denies chemotherapy and radiation
therapy. Generalized bony pain, and high
calcitonin levels.
CT PET PET/CT
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PET/CT in Management Change
CT PET
PET/CT
ACB 01/07/05
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PET/CT in Management Change
ADVANTAGES OF PET/CT OVER PET (2)

• PET/CT identifies other physiologic
  accumulations
• - brown adipose tissue
• - muscles gtgt increased specificity
• Goerres GW et al. J Nucl Med 2004 45 66S-71S
• Cohade C et al. J Nucl Med 2003 44 170-6

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PET/CT in Management Change
Brown Fat Uptake
CT PET
PET/CT
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PET/CT in Management Change
Brown Fat Uptake and Solitary Lesion
CT PET
PET/CT
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PET/CT in Management Change
Brown Fat Uptake and Diazepam
BEFORE
AFTER
CT PET
PET/CT
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PET/CT in Management Change
BREAST CARCINOMA

• VLRLM, 49 y.o. female
• Hx Left breast cancer for 10 years, with total
  mastectomy and axillary node dissection.
  Submitted to chemotherapy and radiotherapy.
  Developed bone, brain, pleural and peritoneal
  metastases, but pleural effusion has been
  negative for malignancy. CA15 784 (very
  high)
• PET/CT For staging

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BREAST CARCINOMA
VRLRM 05/30/03 0130 PM
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VLRLM 05/30/03 130PM
CT PET PET/CT
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PET/CT in Management Change
BREAST CARCINOMA

• Staging and Management Change
• 1) These images change staging in up to 36 of
  patients (28 upstaging, 8 downstaging)
• 2) Unsuspected lymph nodes or metastases found
  in up to 20 of patients
• 3) Management change in up to 58 of patients
• Yap CC et al. J Nucl Med 2001 42 1334-37

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PET/CT in Management Change
BREAST CARCINOMA

• MSFKD, 46 y.o. female
• Hx  Left sided mastectomy 6 years ago, followed
  by chemotherapy. Three years ago,
  bony metastases were found and patient was
  submitted to additional chemotherapy until 1
  month ago. Radiation therapy of the sternum
  was begun and ended last month. She also
  had a pathologic fracture of the left iliac
  bone.
• PET/CT For staging 

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MSFKD 11/07/03
CT PET PET/CT
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PET/CT in Management Change
BREAST CARCINOMA

• Tumor Recurrence
• 1) Sensitivity of up to 100 for locoregional
  recurrence
• 2) Complementary to bone scintigraphy it is
  more sensitive for lytic or marrow lesions,
  and bone scintigraphy is more sensitive for
  blastic lesions
• 3) Shorter survival for patients with pure
  lytic lesions than for patients with mixed
  or sclerotic lesions
• Eubank WB et al. Radiographics 2002 22 5-17
• Hathaway PB et al. Radiology 1999 210 807-14
• Cook GJ et al. J Clin Oncol 1998 16 3375-79

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PET/CT in Management Change
COLORECTAL CARCINOMA

• FA, 53 y.o. male
• Hx Transverse colon carcinoma operated on in
  September 2002. Liver metastases demonstrated
  during workup. Submitted to chemotherapy through
  February 2003. No radiotherapy. In March,
  2003, new surgery and radioablation of 18 liver
  metastases. In May, 2003, submitted to
  131I-lipiodol protocol and intra-arterial
  chemotherapy. Patient is now doing well.
• PET/CT For investigation of extent of disease

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FA 06/06/03
CT PET PET/CT
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FA 06/06/03
CT PET PET/CT
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PET/CT in Management Change
COLORECTAL CARCINOMA

• SBK, 57 y.o. male
• Hx Sigmoid colon carcinoma operated on 3 yrs
  ago, with liver metastases. Radio-ablation of
  the lesions followed by chemotherapy. CEA is
  high.
• CT (dedicated) Unable to distinguish viable
  tumor from fibrosis.
• PET/CT To evaluate tumor viability

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SBK 04/07/2004
CT PET PET/CT
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PET/CT in Management Change
COLORECTAL CARCINOMA

• Management Change
• Changed therapy in 68 of patients, especially
  by demonstrating unknown sites of disease
  (upstaging).
• Meta J et al. J Nucl Med 2001 42 586-90

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PET/CT in Management Change
COLORECTAL CARCINOMA

• Management Change
• In 204 oncologic patients (lung, colorectal,
  stomach, malignant melanoma, breast, kidney,
  bladder, uterus) the interpretations of CT, PET
  and PET/CT were compared
• PET/CT provided additional data in 49 of them
  changed 10 of equivocal lesions to benign and of
  5 to malignant localized precisely tracer
  uptake in 6 of patients and retrospectively
  localized lesions in 8 changed clinical
  management in 14 of patients.
• Bar-Shalom R et al., J Nucl Med 2003 441200-09

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PET/CT in Management Change
G-U MALIGNANCIES

• Several studies have shown variable results.
• Limitations to dedicated PET (non-PET/CT)
• - marked renal excretion of 18F-FDG poses a
  problem to identify kidney, ureter, bladder
  and prostate tumors and lymph nodes closer to
  the bladder - large amounts of
  glucose-6-phosphatase, that converts18F-FDG-6-p
  hosphate back into18F-FDG with its excretion
  from the tumor cell
• Hain SF, Maisey MN. BJU Int 2003 92159-64
• Shvarts O et al. Cancer Control 2002 9
  335-42
• Janzen NK et al. Urol Oncol 2003 21 317-26
• Van der Heijden AG, Witjes JA. Curr Opin Urol
  2003 13 389-95
• De Santis M et al. J Clin Oncol 2004 22
  1034-39
• Hricak H et al. Semin Oncol 2003 30 616-34
• Nunez R et al. J Nucl Med 2002 43 46-55

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PET/CT in Management Change
PROSTATE CARCINOMA

• 18F-FDG uptake is higher in more aggressive
  tumors and correlates with Gleason scores and to
  some extent with PSA levels
• Agus DB et al. Cancer Res 1998 15 583009-14
• Seltzer MA et al. J Urol 19991621322-8
• Limiting factors for detection of primary tumor
• - variable uptake according to aggressiveness
• - high levels of bladder radioactivity
• - outdated reconstruction techniques
• Hofer C et al. Eur Urol 1999 36 31-5
• Effert PJ et al. J Urol 1996 155 994-8

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PET/CT in Management Change
PROSTATE CARCINOMA

• CMS, 46 y.o. male
• Hx Prostate adenocarcinoma diagnosed a week ago
  and since then on
  hormone therapy. No other therapy has been
  attempted.
• No other imaging studies available.
• PET/CT For therapy decision.
• PMH Hypothyroidism

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CT PET PET/CT
CMS 03/29/05
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AFTER FUROSEMIDE
CORONAL
SAGITTAL
TRANS-AXIAL
CT PET
PET/CT
CMS 03/29/05
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AFTER FUROSEMIDE
CORONAL
SAGITTAL
TRANSAXIAL
CT PET PET/CT
CMS 03/29/05
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IPM 07/14/03
53
IPM 07/17/03
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PET/CT in Management Change
BLADDER CARCINOMA

• Accuracy for bladder cancer staging has been
  about 50 for CT and 75 for MRI
• 18F-FDG PET has been considered not useful due to
  urinary excretion of the radiopharmaceutical,
  with sensitivity of 67 and specificity of 85
• Bachor R et al. Urologe A. 1999 38 46-50
• In our laboratory
• - 10 pts with invasive tumors
• - PET/CT images before and after i.v.
  furosemide hydration
• - lesions detected in 6/10 (biopsy proven)
• - 60 pts restaged
• - CT showed wall thickening in only 4

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PET/CT in Management Change
BLADDER CARCINOMA

• JCSE, 80 y.o. male
• Hx Bladder carcinoma detected in May, 2003,
  underwent resection at the time.
  Recurrence in August, 2003 and an additional
  resection, now comprising 2/3 of the bladder.
• US (abdomen) Normal
• PET/CT For restaging

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BEFORE FUROSEMIDE
AFTER FUROSEMIDE
AFTER FUROSEMIDE
AFTER FUROSEMIDE
JCSE
CT PET PET/CT
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PET/CT in Management Change
LYMPHOMAS

• UGAS, 51 y.o. male
• Hx Intermediate type non-Hodgkins lymphoma
  stage IV, diagnosed 14 days ago. Anatomic
  imaging studies showed abdominal involvement
  only. A bone marrow biopsy was positive. Patient
  now complains of fatigue
• PET/CT For staging.

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LYMPHOMAS
3D IMAGES
UGAS 03/17/04
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PET/CT in Management Change
LYMPHOMAS

• Hodgkins Disease
• Conventional images rely essentially on the
  dimensions of lymph nodes for decision on the
  presence of tumor
• Unfortunately, normal-sized lymph nodes may
  contain tumor and enlarged lymph nodes may only
  be fibrotic or reactive
• In addition, lymphomatous infiltration of the
  liver, spleen and bone marrow cannot be detected
  with accuracy by conventional imaging
• Moog F et al. Radiology 1998 206 475- 81

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PET/CT in Management Change
LYMPHOMAS

• MGIB, 59 y.o. female
• Hx Abdominal non-Hodgkins lymphoma, treated
  with chemotherapy only. Denies radiation therapy
• PET/CT For pre-therapy staging and for
  evaluation of residual mass after therapy

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PRE-CHEMO
MGIB 10/22/2003
CT PET PET/CT
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POST-CHEMO
MGIB 01/06/2004
CT PET PET/CT
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PET/CT in Management Change
LYMPHOMAS

• HCC, 41 y.o. male
• Hx Hodgkins lymphoma diagnosed in October,
  2003, with lesions in the mediastinum, right
  axilla, abdomen and pelvis. Submitted to
  chemotherapy from November, 2003 through April,
  2004, the last cycle one month ago.
• PET/CT For staging.

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PRE- CHEMO
CT PET PET/CT
HCC 11/07/2003
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PRE- CHEMO
3D PET
HCC 11/07/2003
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POST- CHEMO
CT PET PET/CT
HCC 05/26/2004
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PET/CT in Management Change
LYMPHOMAS

• Management Change
• May change staging in 8 to 44 of patients
  (upstaging or downstaging)
• May change clinical management in up to 62 of
  patients
• May be positive in up to 50 of patients
  considered in complete remission
• Moog F et al. Radiology 1997 203 795- 800
• Romer W et al. Clinical Positron Imaging 1998 1
  101-10
• Moog F et al. Radiology 1998 206 475- 81
• Bangerter M et al. Ann Oncol 1998 9 1117-22
• Bangerter M et al. Acta Oncol 1999 38 799-804
• Schöder H et al. J Nucl Med 2001 42 1139-43

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PET/CT in Management Change

• How was it possible to interpret
• PET WITHOUT CT
• until now?

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PET/CT in Management Change

• How was it possible to interpret
• CT WITHOUT PET
• until now?