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Positron Emission Tomography (PET) Jann Mortensen Department of Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark. E-mail: [email protected] 8th Annual Congress, Thoracic imaging in lung diseases, April 30th 2005. annihilation photon. g. electron/positron annihilation. b -.

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Positron emission tomography pet jann mortensen

Positron Emission Tomography (PET)

Jann Mortensen

Department of Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark

E-mail:

[email protected]

8th Annual Congress, Thoracic imaging in lung diseases, April 30th 2005


Positron emission tomography pet jann mortensen

annihilation

photon

g

electron/positron

annihilation

b-

b+

g

annihilation

photon

Decay with positron

emission

Princip of Positron Emission Tomography

Radioactive glucose ligand:

18Fluoro-Deoxy-Glucose

1+

0.0

(109.77m)

EC1,

0+

0.0

(stable)


Positron emission tomography pet jann mortensen

Positron Emission tomography (PET)


Positron emission tomography pet jann mortensen

Normal cells use glucose

GLU

GLU

GLU-6-phoshate

CO2+H20

hexokinase

FDG

FDG-6- phoshate

FDG

Glut 1 & 3


Positron emission tomography pet jann mortensen

(Warburg O. 1930, 129-169)

Cancer cells use much glucose

*

Also high amino acid

and nucleic acid use

GLU

GLU

GLU-6-phoshate

CO2+H20

FDG

FDG-6- phoshate

FDG

Metabolic trapping

Glut 1 & 3


Positron emission tomography pet jann mortensen

Physiology of FDG tumor uptake

FDG signal in tumor is dependent on 1) delivery (blood flow),

2) transport into the cells, and 3) phosporylation

FDG tumor uptake ~ number of viable cancer cells


Normal fdg pet

Normal FDG-PET

  • Visual assessment


Physiologic and patologic fdg metabolism

Physiologic and patologic FDG metabolism

  • SUV (standard uptake value) = tumor uptake in relation to mean body uptake

    • Correlates with degree of malignancy

    • (Cut-off value > 2.5 SUV ~ malignancy)

MIP 3-D projection

Colour scale ~SUV


Positron emission tomography pet jann mortensen

Prognostic information from

tumor metabolism

PET predicts survival

SUV Median survival

low uptake < 10 2 yr

high uptake > 101 yr

+ large mass >3 cm½ yr

Ahuja et al. Cancer 1998; 83 ; 918-24

In multivariate analysis,the SUV was independently predictive

of disease-free and overallsurvival

Vansteenkiste J, Fischer BM, Dooms C, Mortensen J. Lancet Oncol 2004; 5: 531–40


Performing a pet study

Performing a PET study

  • Patient preparation: > 4 h fast, drink (but no sugar)

  • Blood sample for glucose (no hyperglycaemia)

  • 400 MBq 18-F FDG i.v., rest ½-1 h

  • Scan time:

    • PET: regional ~ 15-30 min, whole body scan 60 min

    • PET/CT:regional < 15 min, whole body scan <30 min

PET

CT


Positron emission tomography pet jann mortensen

Low dose CT

PET

Fused PET + CT


Positron emission tomography pet jann mortensen

CT

PET

Fused PET + CT

Anato-metabolic imaging


Indications pet in pulmonary disease

Cancer

Infection & inflammation

Indications: PET in pulmonary disease


Indications pet in pulmonary disease1

Cancer @

Pulmonary nodules

Staging (NSCLC)

Relaps and re-staging

Treatment monitoring

SCLC

Mesothelioma

[Radiation field planning]

Indications: PET in pulmonary disease

@ PET costs covered by US Medicare


Indications pet in pulmonary disease2

Cancer @

Pulmonary nodules

Staging (NSCLC)

Relaps and re-staging

Treatment monitoring

SCLC

Mesothelioma

[Radiation field planning]

Infection & inflammation*

Localisation and monitoring of activity:

Sarcoidosis

AIDS (opportunistic infections and malignancy)

Fever of unknown origin

Lung abscess

Tuberculosis, Actinomycosis, Histoplasmosis, Invasive aspergillosis

Vasculitis (Wegener, Takayasu..)

Radiation induced inflammation

Indications: PET in pulmonary disease

@ PET costs covered by US Medicare

* = Sem Nucl Med 2002 ;32: 293-321


Main indication fdg pet in spn

Main indication: FDG-PET in SPN

  • Single pulmonary nodule/mass on CT which is borderline for malignancy

  • cannot be easily biopsied or inconclusive biopsy

    • Malignant or benign ?

  • Indication supported by > 16 studies in > 1000 patients with histologic/long-term follow-up

  • Sensitivity 0.96

  • Specificity 0.78

  • PPV and NPV >0.90

    • Size: 1-4 cm

    • 1474 nodules (JAMA 2001; 285: 914-24)

      • Only 8 nodules <1 cm: 3 TP, 2 TN, 3 FN

      • Diagnostic value in < 1 cm small nodules ?

Lancet Oncol 2001;2:659-66


Case 1 57 y o m with copd

Case 1: 57 y-o-m with COPD

9 mm nodule found on high-resolution CT

18F-FDG PET


Positron emission tomography pet jann mortensen

Case 1: 57 y-o-m with COPD

transaxial coronal saggital

Diagnosis and staging

(PET suggests T1 N0 M0)

attenuation corrected

RH - PET / jm (ap)


Fdg pet in small nodules 10 mm

FDG PET in small nodules (<10 mm)

  • The interpretation of FDG-PET findings in subcentimetric nodules is at present unsolved.

    • [Vansteenkiste JF. Lung Cancer 2004; 45: 29-30].

  • 4 new studies on > 100 SPN in the litterature

    • 3 positive and 1 negative about the value of FDG PET

  • [Lung Cancer 2004; 45:19—27] [Nucl Med Commun 2004; 25: 3-9]

  • [Am J Respir Crit Care Med. 2005 (in press)][Lancet 2003;362:593-79]

  • Studies in progress on value of PET in low-dose CT screening


    Fdg pet in large nodules

    FDG PET in large nodules

    • FDG-PET can discriminate between malignant / benign ≥ 10 mm solid pulmonary nodules !

    • FDG-PET has a high negative predictive value, can correctly exclude malignancy in the vast majority of nodules seen in daily practice.

    • A surgical procedure can be avoided,

    • A repeat CT after 3-12 months can be used to confirm the absence of growth (ie. benignity).

    Lancet Oncol 2001; 2: 659-66

    Lung Cancer 2004; 45: 29-30.


    Positron emission tomography pet jann mortensen

    Main indication : Staging in NSCLC

    T NM status (in one exam.)

    • Conventional staging is inaccurate. After presumably radical treatment, 20% develop an early distantrelapse.

    • [Lancet 1996;347:649–653].

    Indication supported by studies in

    > 1500 patients

    with histologic/long-term follow-up

    Lancet Oncol 2001;2:659-66


    Impact of pet in lung cancer

    Impact of PET in lung cancer

    • PET changes stage in 35% of patients (N=894, 16 studies)

      • Usually the PET stage is higher than with usual work-up incl. CT

        • Due to local (N2 eller N3) metastasis or extra-pulmonary metastasis

      • ie. operation is unnecessary

      • change in therapy to chemotherapy and / or radiation treatment

        • Semin Nucl Med 2002, 32:240-71

    • PET is cost effective in lung cancer

      • Both for diagnosis of single pulmonary nodules and for Staging

      • References: (Gambhir J Clin Oncol 1998; 16: 2113-2125) (Dietlein Eur J Nucl Med 2000; 27: 1441-56) (Gould ARRDCCM 2001) (Plus study)


    Randomised study of pet staging

    Randomised study of PET staging

    • Effect parameter: no. unneccesary thoracotomy´s

    • 188 ptt. usual work-up +/- PET, 1 yr follow-up

    • 9 Deutch hospitals (1 dedicated PET center)

    • PET reduced the no. unneccesary thoracotomy´s:

      • PET 32 (41%) , + PET 18 ptt (21%)

    • For each 5 PET scans one unneccesary thoracotomy was avoided

      • reduced cost per patient with PET: > 1.000 EURO

    (PLUS study. Lancet 2002; 359: 1388-92)


    Positron emission tomography pet jann mortensen

    Prospective study of preoperative staging with PET vs. standard staging (CT, ultrasound, bone scanning)

    • 102 patients with resectable NSCLC, 6 months follow-up,

    • histopathological reference.

  • (N) metastasisSensitivitySpecificity

  • PET 91 %86 %

  • CT 75 %66 %

  • (M) metastasis: PET identified distant metastases not found

    by standard methods in 11 of 102 patients:

    PET identified a different stage in 62 patients:

    stage was lowered in 20 and raised in 42

    Pieterman et al. N Engl J Med 2000;343:254-61


    Fdg pet for extrathoracic metastasis

    FDG PET for extrathoracic metastasis

    • 40% with NSCLC have distantmetastases at presentation, most often in the

    • adrenal glands,bones, liver, or brain [Ann Thorac Surg 1996;62:246–250].

    • Adrenal glands: 10% of NSCL have enlarged adrenal glands on CT, 2/3 being benign.

    • PET has high sensitivity (>92%) and specificity (80%–100%) -> reduces number of unnecessary adrenal biopsies.

    • Bone: Bone scintigraphy good sensitivity (90%), low specificity (±60%),

    • PET good sensitivity (90%), but higher specificity (98%)and accuracy (96%).

    • Liver:US and/or CT remain thestandard imaging techniques for the liver. No good comparisons studies. Additional diagnosticinformation by PET combined with CT, in thedifferentiation of hepatic lesions that are indeterminate onconventional imaging.

    • Brain:PET low sensitivity (60%) not suited for the detection of brain metastases.

    The Oncologist 2004; 9 (6): 633-43


    Fdg pet for extrathoracic metastasis1

    FDG PET for extrathoracic metastasis

    • 40% with NSCLC have distantmetastases at presentation, most often in the

    • adrenal glands,bones, liver, or brain [Ann Thorac Surg 1996;62:246–250].

    • Adrenal glands: 10% of NSCL have enlarged adrenal glands on CT, 2/3 being benign.

    • PET has high sensitivity (>92%) and specificity (80%–100%) -> reduces number of unnecessary adrenal biopsies.

    • Bone: Bone scintigraphy good sensitivity (90%), low specificity (±60%),

    • PET good sensitivity (90%), but higher specificity (98%)and accuracy (96%).

    • Liver:US and/or CT remain thestandard imaging techniques for the liver. No good comparisons studies. Additional diagnosticinformation by PET combined with CT, in thedifferentiation of hepatic lesions that are indeterminate onconventional imaging.

    • Brain:PET low sensitivity (60%) not suited for the detection of brain metastases.

    The Oncologist 2004; 9 (6): 633-43


    Positron emission tomography pet jann mortensen

    PET/CT in lung cancer

    ”PET/CT will improve staging in 20- 40 % of lung cancer patients”

    Lardinois D et al.

    N Engl J Med 2003; 348: 2500-7

    Cerfolio RJ et al. Ann Thorac Surg 2004; 78: 1017–23

    A randomised study in progress in Copenhagen


    Positron emission tomography pet jann mortensen

    Bone metastasis with normal CT


    Value of pet in lung cancer

    Value of PET in lung cancer

    • Sensitivity ~ 96 % (SPN); ~ 73% (N staging)

    • Specificity ~ 78 % (SPN), ~ 93% (N staging)

    • Reasons for false negative

      • Small size (resolution 6 mm, movement)

      • Well-differentiated tumors:

        • Adenocarcinoma

        • Carcinoids (Neuroendocrine tumors)

        • Broncioalveolar carcinoma (BAC)

      • Dysregulated diabetes, insufficient fast

    • Reasons for false positive

      • Infection / inflammation (Indication per se)


    Increased fdg pet uptake can be seen in benign pulmonary conditions

    Increased FDG-PET uptake can be seen inbenign pulmonary conditions

    • Infections

      • Lung abscess

      • Tuberculosis (and M avium intracellulare)

      • Bacterial pneumonia, Actinomycosis, Histoplasmosis, Invasive aspergillosis, aspergilloma, blastomycosis

    • Inflammatory lesions

      • Sarcoidosis

      • Vasculitis: Wegeners granulomatosis, takayasu arteritis, etc

      • Pneumoconiosis (silicosis, coal workers-, fibrosis)

      • Rheumatoid arthritis, sclerosing mediastinitis

      • Amyloidosis, Idiopathic pulmonary fibrosis

      • Bronciolitis oblitarative organising pneumonia (BOOP),etc

    • Benign neoplasm (-chondrohamartoma)

    • Iatrogenic disorders

      • Radiation induced pneumonitis, biopsy, rib fractures, etc

    Case stories

    Sem Nucl Med 2002;32(4):246 & 293-321


    Increased fdg pet uptake can be seen in benign mediastinal adenopathies z

    Increased FDG-PET uptake can be seen inbenign mediastinal adenopathies(Z)

    • Granulomatosis and silicosis (Inflammation)

      • Sarcoidosis

      • Anthrasilicosis

    • Infections

      • Histoplasmosis,

      • Tuberculosis (and M avium intracellulare)

      • Actinomycosis, etc.

    • Benign neoplasm (-thymoma, teratoma, swannoma)

    • Iatrogenic disorders (Radiation related changes)

    Case stories

    (Z) Yet, only a minority with these conditions have a high FDG uptake

    Sem Nucl Med 2002;32(4): 293-321


    Positron emission tomography pet jann mortensen

    FDG PET in active tuberculosis

    • TB in a 58-year-old man. (A) chest radiograph shows two nodules (b) coronal FDG PET scan shows increased uptake (solid arrow) in the left upper lobe nodules (SUV 4).

    • Radiology 2000 6:117-21


    Sarcoidosis

    Sarcoidosis

    Monitoring:

    Localisation of activity

    in- and outside lungs:

    Before treatment:

    After inhaled steroid:

    After prednisolone:

    • Milman N, Mortensen J, Sloth C. Respiration. 2003;70:408-13.


    Newer indications for pet in lung cancer

    Newer indications for PET in lung cancer

    PET predicts survival

    SUVmedian survival

    < 10 2 yr

    > 10 1 yr

    + mass >3 cm½ yr

    Ahuja et al. Cancer 1998; 83 ; 918-24

    • Prognostic information from SUV

    • Evaluation of treatment effect ->

    • PET/CT for planning of radiation field

    • Staging and monitoring SCLC ->

    • Staging and diagnosis of Mesothelioma


    Newer indications for pet in lung cancer1

    Newer indications for PET in lung cancer

    • Prognostic information from SUV

    • Evaluation of treatment effect ->

    • PET/CT for planning of radiation field

    • Staging and monitoring SCLC ->

    • Staging and diagnosis of Mesothelioma


    Newer indications for pet in lung cancer2

    Newer indications for PET in lung cancer

    • Prognostic information from SUV

    • Evaluation of treatment effect ->

    • PET/CT for planning of radiation field

    • Staging and monitoring SCLC ->

    • Staging and diagnosis of Mesothelioma

    • PET/CT guided RT improves radiation dose to the tumor

    • and metastases and reduces dose to adjacent normal tissue

      • No studies with patient outcome yet


    Newer indications for pet in lung cancer3

    Newer indications for PET in lung cancer

    • Prognostic information from SUV

    • Evaluation of treatment effect ->

    • PET/CT for planning of radiation field

    • Staging and monitoring SCLC ->

    • Staging and diagnosis of Mesothelioma


    Newer indications for pet in lung cancer4

    Newer indications for PET in lung cancer

    • Prognostic information from SUV

    • Evaluation of treatment effect ->

    • PET/CT for planning of radiation field

    • Staging and monitoring SCLC ->

    • Staging and diagnosis of Mesothelioma

    J Nucl Med. 1999 Aug;40(8):1241-5.

    Semin Oncol. 2002 Feb;29(1):26-35.

    • FDG PET for:

    • Guiding of biopsy

    • Staging (extrathoracic or contralateral metastasis)


    Help from a pet scan

    Help from a PET-scan

    • A positive PET focus indicates malignancy

      • but needs histological proof (to avoid false positive)

      • PET or PET/CT guided biopsy possible

  • A negative PET focus indicates benignancy

    • A solitary pulmonary nodule is either benign or very slowly growing cancer (no or CT control 6-12 months for growth)

    • Staging, no metastasis found, refer to operation.


  • Conclusion

    Conclusion

    • Single Pulmonary Nodules

      • Differentiate between benign/malignant indeterminate SPN

        • if biopsy is difficult / nondiagnostic

        • confirm benignity with CT follow-up

      • the uptake predicts prognosis (high metabolism -> bad prognosis)

    • StagingRegional (N) and distant (M) metastases:

      • Addition of PET improves conventional staging (CT+US+ bone scintigraphy)

      • PET changes stage and treatment in ~35 % of patients

        • Detects unexpected distant metastases in ~14 %

        • Exclusion of malignancy in ~5 % (can be operated)

        • Usually a higher stage is found

        • Avoids unneccesary thoracotomy (in 10-20 %)

        • Mediastinoscopy can be avoided if PET + CT are normal (in non-central tumors)

    • Other indications:

      • Restaging and treatment monitoring, radiation field planning, SCLC, Mesothelioma

      • Localisation & monitoring of infections & inflammatory disorders


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