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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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slide1
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

slide2
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)

slide4
Normal cells use glucose

GLU

GLU

GLU-6-phoshate

CO2+H20

hexokinase

FDG

FDG-6- phoshate

FDG

Glut 1 & 3

slide5
(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

slide6
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

slide9
Prognostic information from

tumor metabolism

PET predicts survival

SUV Median survival

low uptake < 10 2 yr

high uptake > 10 1 yr

+ large mass >3 cm ½ 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

slide11
Low dose CT

PET

Fused PET + CT

slide12
CT

PET

Fused PET + CT

Anato-metabolic imaging

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

slide18
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.

slide21
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)

slide24
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

slide27
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

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

slide32
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

SUV median survival

< 10 2 yr

> 10 1 yr

+ mass >3 cm ½ 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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