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

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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


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


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


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


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)


PET/CT in Brazil: a New Standard

  • 18F-FDG Distribution

    • Sao Paulo

    • Rio de Janeiro

    • Campinas

    • Other cities: Brasília?


Rio de

Janeiro

375 km

90 km


Recife

Goiânia

  • Campinas


PET/CT in Brazil: a New Standard

[F-18]FDG

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


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]


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-phosphatase such as the liver, kidneys and intestines accumulate [18F]-FDG6-PO4 to a lesser extent.


Glucose metabolic pathways

PET/CT in Brazil: a New Standard

GLUCOSE METABOLIC PATHWAYS

hexokinase

Glucose glucoseglucose-6-phosphate

glucose-6-phosphatase

hexokinase

X

18F-FDG 18F-FDG18F-FDG-6-phosphate

glucose-6-phosphatase


BABYCYCLOTRON


PET/CT in Brazil: a New Standard

Positron Emitters

Radionuclides T ½

Oxygen-15 2 minutes

Nitrogen-1310 minutes

Carbon-1120 minutes

Fluorine-18110 minutes

Iodine-1244.2 days


PRINCIPLE OF POSITRON

EMISSION TOMOGRAPHY

 = 511 keV

Positron

emitter

+

180°

-electron

 = 511 keV


PET / CTSCANNER


Pet ct configuration
PET/CT Configuration

  • CT up front

  • PET moves backwards for maintenance

  • Single tunnel

CT

PET


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 @ 1cm = 4.5 mm

  • FWHM @ 10cm=5.6mm

  • Axial resolution (NEMA 2001): FWHM @ 0cm = 4.2mm      FWHM @ 10cm=5.7mm 

  • CT: 

  • Scanning time: 80 s standard

  • Rotation: 0.8; 1.0; and 1.5 s

  • Slice width: 1, 2, 3, 5, 8 and10mm

  • Minimum slice width: 1 mm

  • High contrast resolution: 0.32 and 0.36 mm


NORMAL

JACO

10/03/2004


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]


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

PET IN CLINICAL ONCOLOGY


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%


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%.


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%


Pet ct in management change

PET/CT in Management Change

ADVANTAGES OF PET/CT OVER PET

  • PET/CT precisely identifies, localizes and delineates size and extent of a lesion:

  • >> essential data for surgical and radiation therapy planning

  • Goerres GW et al. J Nucl Med 2004; 45: 66S-71S


Pet ct in management change1

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


Pet ct in management change2

PET/CT in Management Change

CT PET PET/CT

ACB

01/07/05


Pet ct in management change3

PET/CT in Management Change

ADVANTAGES OF PET/CT OVER PET (2)

  • PET/CT identifies other physiologic accumulations:

  • - brown adipose tissue

  • - muscles >>increased specificity

  • Goerres GW et al. J Nucl Med 2004; 45: 66S-71S

  • Cohade C et al. J Nucl Med 2003; 44: 170-6


  • Pet ct in management change4

    Brown Fat Uptake

    PET/CT in Management Change

    CT PET PET/CT


    Pet ct in management change5

    Brown Fat Uptake and Solitary Lesion

    PET/CT in Management Change

    CT PET PET/CT


    Pet ct in management change6

    Brown Fat Uptake and Diazepam

    PET/CT in Management Change

    BEFORE

    AFTER

    CT PET PET/CT


    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


    BREAST CARCINOMA

    VRLRM

    05/30/03

    01:30 PM


    VLRLM 05/30/03

    1:30PM

    CT PET PET/CT


    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


    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


    MSFKD

    11/07/03

    CT PET PET/CT


    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 sensitivefor 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


    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


    FA

    06/06/03

    CT PET PET/CT


    FA

    06/06/03

    CT PET PET/CT


    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


    SBK

    04/07/2004

    CT PET PET/CT


    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


    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., JNucl Med 2003; 44:1200-09


    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-phosphate back into18F-FDG with its excretion from the tumor cell

      Hain SF, Maisey MN.BJU Int 2003; 92:159-64

      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


    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; 58:3009-14

      Seltzer MA et al.J Urol 1999;162:1322-8

    • 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


    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


    CT PET PET/CT

    CMS

    03/29/05


    AFTER FUROSEMIDE

    CORONAL

    SAGITTAL

    TRANS-AXIAL

    CT PET PET/CT

    CMS

    03/29/05


    AFTER FUROSEMIDE

    CORONAL

    SAGITTAL

    TRANSAXIAL

    CT PET PET/CT

    CMS

    03/29/05


    IPM

    07/14/03


    IPM

    07/17/03


    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


    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


    BEFORE FUROSEMIDE

    AFTER FUROSEMIDE

    AFTER FUROSEMIDE

    AFTER FUROSEMIDE

    JCSE

    CT PET PET/CT


    PET/CT in Management Change

    LYMPHOMAS

    • UGAS, 51 y.o. male

    • Hx: Intermediate type non-Hodgkin´s 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.


    LYMPHOMAS

    3D IMAGES

    UGAS

    03/17/04


    PET/CT in Management Change

    LYMPHOMAS

    • Hodgkin´s 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


    PET/CT in Management Change

    LYMPHOMAS

    • MGIB, 59 y.o. female

    • Hx: Abdominal non-Hodgkin´s lymphoma, treated with chemotherapy only. Denies radiation therapy

    • PET/CT: For pre-therapy staging and for evaluation of residual mass after therapy


    PRE-CHEMO

    MGIB

    10/22/2003

    CT PET PET/CT


    POST-CHEMO

    MGIB

    01/06/2004

    CT PET PET/CT


    PET/CT in Management Change

    LYMPHOMAS

    • HCC, 41 y.o. male

    • Hx: Hodgkin´s 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.


    PRE-

    CHEMO

    CT PET PET/CT

    HCC

    11/07/2003


    PRE-

    CHEMO

    3D PET

    HCC

    11/07/2003


    POST-

    CHEMO

    HCC

    05/26/2004

    CT PET PET/CT


    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


    PET/CT in Management Change

    • “How was it possible to interpret

    • PET WITHOUT CT

    • until now?”


    PET/CT in Management Change

    • “How was it possible to interpret

    • CT WITHOUT PET

    • until now?”


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