Gino Pepe

Medicina Nucleare – PET H.SanRaffaele IRCCS - Milano

L'uso della PET nella diagnosi precoce L'uso della PET nella diagnosi precoce

e la valutazione del SUV e la valutazione del SUV

come indicatore di prognosi come indicatore di prognosi

[18F]FDG PETCT

[18F]FDG-PET

Why [18F]FDG-PET in tumors?

Elevated glucose metabolism in tumor

Why [18F]FDG-PET in tumors?

Elevated glucose metabolism in tumor

[18F]FDG is a glucose analog

Why [18F]FDG-PET in tumors?

Elevated glucose metabolism in tumor

[18F]FDG is a glucose analog

[18F]FDG uptake into viable neoplastic cells

Why [18F]FDG-PET in tumors?

[[1818F]FDG PET: APPLICATION IN LUNG CANCERF]FDG PET: APPLICATION IN LUNG CANCER

Differentiating benign from malignant lesions (SPN)

Staging N and M and re-staging for therapy planningStaging N and M and re-staging for therapy planning

Predicting and monitoring response to therapyPredicting and monitoring response to therapy

Solitary Pulmonary Nodule (SPN)Solitary Pulmonary Nodule (SPN)

Solitary lung lesion < 3 cm in diameterSolitary lung lesion < 3 cm in diameter

20% - 40% of SPN are malignant20% - 40% of SPN are malignant

Initial presentation in 20% - 30% of lung cancerInitial presentation in 20% - 30% of lung cancer

Coleman et al. J Nuc Med 1999

Visual AnalysisVisual Analysis

Quantitative analysisQuantitative analysis

[[1818F]FDG PETF]FDG PET

Measure of metabolic activity of SPNMeasure of metabolic activity of SPN

SUV = 7.3

CT [18F]FDG PETCT [18F]FDG PET

Visual Analysis: Visual Analysis: nodule activity vs mediastinal blood pool activitynodule activity vs mediastinal blood pool activity

Quantitative analysisQuantitative analysis

[[1818F]FDG PETF]FDG PET

Measure of metabolic activity of SPNMeasure of metabolic activity of SPN

SUV = 7.3

CT [18F]FDG PETCT [18F]FDG PET

Visual Analysis: Visual Analysis: nodule activity vs mediastinal blood pool activitynodule activity vs mediastinal blood pool activity

Quantitative analysisQuantitative analysis

[[1818F]FDG PETF]FDG PET

Measure of metabolic activity of SPNMeasure of metabolic activity of SPN

SUV = 7.3

CT [18F]FDG PETCT [18F]FDG PET

[[1818F]FDG PETF]FDG PET

Measure of metabolic activity of SPNMeasure of metabolic activity of SPN

Visual AnalysisVisual Analysis

Quantitative analysis: Quantitative analysis: SUV (standardized uptake value)SUV (standardized uptake value)

SUV = 7.3

CT [18F]FDG PETCT [18F]FDG PET

Standardized Uptake Value = SUV

– SUVBW = Ct/(ID/BW) = (kBq/ml) / (MBq/Kg)

– SUVLBM = Ct/(ID/LBM) = (kBq/ml) / (MBq/Kg)

• LBM uomini =1.1 * W - 128 *(W/h)2

• LBM donne = 1.07 * W - 148 *(W/h)2

– SUVBSA = Ct/(ID/BSA) = (kBq/ml) / (MBq/m2)

• BSA = 0.007184 * W 0.425 * h 0.725

[[1818F]FDG PETF]FDG PET

Measure of metabolic activity of SPNMeasure of metabolic activity of SPN

Visual AnalysisVisual Analysis

Quantitative analysis: Quantitative analysis: SUV (standardized uptake value)SUV (standardized uptake value)

SUV = 7.3

CT [18F]FDG PETCT [18F]FDG PET

[[1818F]FDG PETF]FDG PET

Measure of metabolic activity of SPNMeasure of metabolic activity of SPN

Visual AnalysisVisual Analysis

Quantitative analysis: Quantitative analysis: SUV (standardized uptake value)SUV (standardized uptake value)

SUV = 7.3

CT [18F]FDG PET

SUV = 7.9

CT [18F]FDG PET

[[1818F]FDG PETF]FDG PET

VisualVisual 100100 69 69 9090 100100 9292

SUVSUV 96 96 69 69 9090 85 85 8989

SensSens SpecSpec PPVPPV NPVNPV AccAcc

Hain SF et al. Eur J Nucl Med 2001

No difference between visual vs. quantitative analysis

A SPN with SUV more than 2.5 is considered to be malignant

Lung cancer is hypermetabolic

CT

Fused

HSR - Milano

[18F]FDG PET

SPN: 1.2 cm in diameter

HSR - Milano

SPN: 1.4 cm in diameter

[18F]FDG PETCT

CT- PET

AuthorsAuthors SensitivitySensitivity Specificity Specificity AccuracyAccuracy

Duhaylongsod (1995)Duhaylongsod (1995) 97%97% 82% 82% 92%92%

Bury (1996)Bury (1996) 100% 100% 88% 88% 96%96%

Lowe (1998)Lowe (1998) 98% 98% 69% 69% 89%89%

Prauer (1998)Prauer (1998) 90% 90% 83% 83% 87%87%

Graeber (1999)Graeber (1999) 97% 97% 89% 89% 92%92%

Hung (2001)Hung (2001) 95% 95% 50% 50% 86%86%

Hellwig (2001) (meta-analysis)Hellwig (2001) (meta-analysis) 96%96% 80% 80% --

Gould (2001) (meta-analysis)Gould (2001) (meta-analysis) 97%97% 78%78% --

Hickeson (2002) (using PET-CT)(using PET-CT) 97%97% 82% 82% 92%92%

Accuracy of PET with [18F]FDG in SPN or Pulmonary Opacity

TubercolosisTubercolosis

SarcoidosisSarcoidosis

AspergillosisAspergillosis

HistoplasmosisHistoplasmosis

CryptococcosisCryptococcosis

Inflammatory lesions (mainly granulomas)

Limitations of FDG-PET for Lung Nodule Characterization:

False-positive results

Lesion DimensionLesion Dimension

Histological TypeHistological Type

HyperglycemiaHyperglycemia

Small lesion < 5-6 mmSmall lesion < 5-6 mm

% of viable neoplastic cells % of viable neoplastic cells in SPNin SPN

Limitations of FDG-PET for Lung Nodule Characterization:

False-negative results

[18F]FDG PETCT

Fused

HSR - Milano

R. F. 53 aaLung nodule

4 mm in diameter

?

[18F]FDG PETCT

CT- PET

HSR - Milano

Z. A. 41 aaSPN: 4 mm in diameter

Lesion DimensionLesion Dimension

Histological TypeHistological Type

HyperglycemiaHyperglycemia

CarcinoidCarcinoid

Pure Bronchioloalveolar Pure Bronchioloalveolar Carcinoma (BAC), mucinous Carcinoma (BAC), mucinous ca, neuroendocrine tumorca, neuroendocrine tumor

Well differentiated typeWell differentiated type

Limitations of FDG-PET for Lung Nodule Characterization:

False-negative results

[18F]FDG PET

HSR - Milano

CARCINOID

CT

[18F]FDG PETCT

PET/CT

HSR - Milano

P. G. 68 aaSPN: 10 mm in diameterWell differentiated tumor

[[1818F]FDG PET IN LUNG CANCERF]FDG PET IN LUNG CANCER

SUV and histological typeSUV and histological type

BAC BAC (12)(12) 1.31.3

Well Differentiated Well Differentiated (10)(10) 3.13.1

Moderately differentiated Moderately differentiated (12)(12) 4.34.3

Poorly differentiated Poorly differentiated (4)(4) 5.65.6

Mean SUV

Higashi et al. Nucl Med Comm 2000

[[1818F]FDG PET IN LUNG CANCERF]FDG PET IN LUNG CANCER

FDG uptake in BACFDG uptake in BAC

No [18F]FDG uptake in more than 50% of patients with BAC

85,7% of BAC are negative for Glut-1 (glucose transporter)

expression (Higashi 2000)

[18F]FDG-PET FN

A different PET tracer may solve the problem

Pure Bronchioloalveolar Carcinoma

B. A. 65 aaHSR Milano

SUV = 1.73

[18F]FDG PETCT [11C]Choline PET

Lesion DimensionLesion Dimension

Histological TypeHistological Type

HyperglycemiaHyperglycemia > 200 mg/dl = PET not performed> 200 mg/dl = PET not performed

Limitations of FDG-PET for Lung Nodule Characterization:

False-negative results

VALUTAZIONE DELLA RISPOSTA ALLA TERAPIA

con PET e [18F]FDG NEL TUMORE POLMONARE

113 pazienti con neoplasia polmonare NSC trattati con 113 pazienti con neoplasia polmonare NSC trattati con

chemio o radiochemioterapiachemio o radiochemioterapia

Patz et al Patz et al AJR, 2000AJR, 2000

Differenza significativa nella sopravvivenza tra pazienti con PET positiva e pazienti con PET negativa

Mediana di sopravvivenza12.1 mesi nei pz con PET + dopo terapia

34.2 mesi nell’85% dei pz con PET - dopo terapia

PET Responder (SUV –61%)

Weber et al., J Clin Oncol 2003; 21:2651

FDG-PET: VALUTAZIONE PRECOCE DELLA RISPOSTA ALLA CHEMIOTERAPIA

PR in 20/28 PET responders (71%)

SD o PD in 26/27 PET non responders (96%)

57 pazienti in stadio IIIB o IV studiati con PET prima e dopo I° ciclo di chemio

PET in SPN

• Who: – Patient with indetermined lung nodule

• When: – After a CT study

• Why: – Metabolic characterization of indetermined

lung nodule (benign vs malignant)