PET

Guillermo Gilligan

Jornadas Nacionales de Radiologia Pediatrica 2014

Sociedad Argentina de Pediatria

9 de agosto 2014

PositronEmissionTomographyP E TGuillermo Gilligan

Respuestas de la Imagen Molecular Indicadores precoces de efectividad terapeutica

que pueden mejorar la atencion

••Reduciendo uso de medicacion Reduciendo uso de medicacion

inefectivainefectiva

Imagenes Convencionales = Reduccion tamaño Tumoral, o Imagenes Convencionales = Reduccion tamaño Tumoral, o

desaparicion , o cambio cualitativoTumoraldesaparicion , o cambio cualitativoTumoral

inefectivainefectiva

••Reduciendo procedimientos que no Reduciendo procedimientos que no

ayudan ayudan

••Reduciendo costosReduciendo costos

••Mejorando calidad de vida y sobrevidaMejorando calidad de vida y sobrevida

PILAR DE LAPILAR DE LA

SENSIBILIDAD=SENSIBILIDAD=

Capacidad deCapacidad de

concentracionconcentracion

MAPA DE LA DISTRIBUCION

CORPORAL DE LA HEXOQUINASA

TUBERCULOSIS

SARCOIDOSIS

ENFERMEDADES GRANULOMATOSAS

MICOSIS SISTEMICAS PROFUNDAS

OSTEOMIELITIS(especialmente con

Injuria estructural osea o hueso violado)Injuria estructural osea o hueso violado)

PET EN INFLAMACION E INFECCION

TAKAYASU

IMAGEN FUNCIONAL CON IMAGEN FUNCIONAL CON

PET PARA SARCOMAS

IMAGEN FUNCIONAL CON PET en Sarcomas

Aplicaciones

• Benigno versus maligno

• Gradacion

• Guia para obtener la mejor muestra biopsia• Guia para obtener la mejor muestra biopsia

• Estadificacion

•Monitoreo terapeutico

• Reestadificacion ( recurrencia local )

June 2012, Volume 198, Number 6

Nuclear Medicine and Molecular Imaging

Original Research

Correlating Metabolic Activity on 18F-FDG PET/CT With Histopathologic Characteristics of Osseous and

Soft-Tissue Sarcomas: A Retrospective Review of 136 Patients

Rajan Rakheja1, William Makis2, Sonia Skamene1, Ayoub Nahal3, Fadi Brimo3, Laurent Azoulay4 5,

Jonathan Assayag6, Robert Turcotte5 and Marc Hickeson1

OBJECTIVE. The objective of our study was to determine whether there is a statistically significant correlation between

metabolic activity of osseous and soft-tissue sarcomas as measured by the maximum standardized uptake value

(SUVmax) on 18F-FDG PET/CT and histopathologic characteristics such as mitotic counts, the presence of necrosis,

and the presence of a myxoid component

MATERIALS AND METHODS. We retrospectively evaluated 238 consecutive patients with known soft-tissue or osseous

sarcoma who underwent 18F-FDG PET/CT for initial staging or assessment for recurrence of disease. The SUVmax of each

primary or of the most intense metastatic lesion was measured and was compared with the histologic data provided in the

final pathology reports

RESULTS. Histopathologic data were available for 136 sarcomas. The median SUVmax values of sarcomas with mitotic

counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00–6.99, 7.00–16.24, and 16.25 or greater were 5.0, 6.6, 10.3, counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00–6.99, 7.00–16.24, and 16.25 or greater were 5.0, 6.6, 10.3,

and 13.0, respectively (p = 0.0003). The median SUVmax for the sarcomas with necrosis (90 patients) was 8.6 and for

those without necrosis (43 patients), 6.0 (p = 0.026). The median SUVmax for the sarcomas without a myxoid component

(118 patients) was 7.7 and with a myxoid component (16 patients) was 6.2 (p = 0.28).

CONCLUSION. There was a statistically significant correlation between the mitotic count significant correlation between the mitotic count

and the SUVmax as well as between the presence of tumor necrosis and the SUVmax.and the SUVmax as well as between the presence of tumor necrosis and the SUVmax.

Although a correlation between the presence of a myxoid component and SUVmax was

shown, it was not found to be statistically significant. These findings improve on the current These findings improve on the current

information in the literature regarding the use of PET/CT for guidance in sarcoma biopsy.information in the literature regarding the use of PET/CT for guidance in sarcoma biopsy.

Correlating the SUVmax with histologic markers that also feature prominently in major

sarcoma grading systems may help improve the accuracy of grading and of prognostication may help improve the accuracy of grading and of prognostication

by allowing the SUVmax to potentially serve by allowing the SUVmax to potentially serve as a surrogate markeras a surrogate marker in these grading in these grading

systems, particularly in cases in which there is interobserver disagreement in the pathologic systems, particularly in cases in which there is interobserver disagreement in the pathologic

diagnosis or in cases in which the sarcoma cannot be properly classified on the basis of diagnosis or in cases in which the sarcoma cannot be properly classified on the basis of

histopathologic evaluation alone.histopathologic evaluation alone.

Grado vs SUV (por percentilo)

n = 89

25% 50% 75%

BEN 1.5 3.8 6.9

PET en Sarcoma

Aplicaciones – Gradacion tumoral

Folpe AL et al. Clin Cancer Res 2000; 6: 1279-1287

BEN 1.5 3.8 6.9

G1 1.55 2.65 4.11

G2 3.40 6.05 10.25

G3 4.22 6.85 19.35

IMAGEN FUNCIONAL CON PET en Sarcoma

Aplicaciones

• Benigno versus maligno

• Gradacion

• Guia para obtener la mejor muestra biopsia(HETEROGENEIDAD)• Guia para obtener la mejor muestra biopsia(HETEROGENEIDAD)

• Estadificacion

•monitoreo terapeutico

• Reestadificacion ( recurrencia local)

• Gran masa en muslo

izquierdo e imagenes de

RMN consistentes con

liposarcoma

• Biopsia guiada hacia la Biopsia guiada hacia la

PET en Sarcoma

Aplicaciones – Guiando biopsia

• Biopsia guiada hacia la Biopsia guiada hacia la

region metabolicamente region metabolicamente

mas elevada confirmo mas elevada confirmo

tumor de alto grado de tumor de alto grado de

malignidadmalignidad

• Multiples metastasis

subcutaneas tambien

detectadas por el PET

IMAGEN FUNCIONAL CON PET en Sarcoma

Aplicaciones

• Benigno versus maligno

• Gradacion

• Guia para obtener la mejor muestra biopsia• Guia para obtener la mejor muestra biopsia

• Estadificacion

•Monitoreo terapeutico

• Reestadificacion ( recurrencia local)

11 a

Osteosarcoma

Femoral

izquierdo

Amputado

99mTcMDP

21 mCi

Fusion FLUORODESOXIGLUCOSA + fluor 18 + T A CT A C

SARCOMA

EWING

TIBIAL

DERECHO

13 a

CONTROL

ANUAL

Tc99m

Mdp

TOTAL

BODY

SARCOMA DE EWING METASTATICO A MANDIBULA DERECHA

PARCIALMENTE EXTRAOSEO

July 2001, Volume 177, Number 1

Pediatric Imaging

Whole-Body MR Imaging for Detection of Bone Metastases in Children and Young Adults

Comparison with Skeletal Scintigraphy and FDG PETHeike E. Daldrup-Link1 2, Christiane Franzius3, Thomas M. Link1 2, Daniela Laukamp1, Joachim Sciuk3,

Heribert Jürgens4, Otmar Schober3 and Ernst J. Rummeny1

OBJECTIVE. The purpose of this study was to compare the diagnostic accuracy of whole-body MR

imaging, skeletal scintigraphy, and 18F-fluorodeoxyglucose (FDG) positron emission tomography

(PET) for the detection of bone metastases in children.

SUBJECTS AND METHODS. Thirty-nine children and young adults who were 2-19 years old and who had Ewing's sarcoma, osteosarcoma, lymphoma, rhabdomyosarcoma, melanoma, and Langerhans' cell

histiocytosis underwent whole-body spin-echo MR imaging, skeletal scintigraphy, and FDG PET for the initial

staging of bone marrow metastases. The number and location of bone and bone marrow lesions diagnosed with

each imaging modality were correlated with biopsy and clinical follow-up as the standard of reference. each imaging modality were correlated with biopsy and clinical follow-up as the standard of reference.

RESULTS. Twenty-one patients exhibited 51 bone metastases. Sensitivities for the detection of bone metastases were 90%

for FDG PET, 82% for whole-body MR imaging, and 71% for skeletal scintigraphy; these data were significantly different (p

< 0.05). False-negative lesions were different for the three imaging modalities, mainly depending on lesion location. Most

false-positive lesions were diagnosed using FDG PET.

CONCLUSION.

Whole-body MR imaging has a higher sensitivity than skeletal

scintigraphy for the detection of bone marrow metastases but

a lower sensitivity than FDG PET

PET en SarcomasAplicaciones - Estadificacion

• TAC superior al FDG PET para detectar MTTS pulmonares (1,2)

• PET puede identificar masas falsamente positivas de TAC

• VPN proporcional a la menor captacion en el tumor primario

• FDG PET tiene mayor sensibilidad que la TAC para metastasis de

1. Franzius C et al Ann Oncol 2001; 12:479-486

2. Lucas JD et al J Bone Joint Surg Br 1998; 80:441-447

3. Franzius C et al Eur J Nucl Med 2000; 27:1305-1311

tejidos blandos (2)

• FDG PET de cuerpo entero superior al centellograma oseo para

metastasis oseas (3)

• FDG-PET NO se discapacita por susceptibilidad al metal o

artefactos generados por metales

• Estudios multiples indican buena seguridad del FDG PET para la

deteccion de recurrencia tardia local

PET en SarcomasAplicaciones– Sospecha de

recurrencia local

Franzius C et al Ann Oncol 2002;13:157-160

Garcia R et al J Nucl Med 1996; 37:1476-1479

el Zeftawy H et al Cancer Biother Radiopharm 2001; 16:37-46

Bredella M et al AJR 2002; 179:1145-1150

Johnson GR et al Clin Nucl Med 2003; 28:815-820

deteccion de recurrencia tardia local

IMAGEN FUNCIONAL CON PET en Sarcomas

Aplicaciones

• Benigno versus maligno

• Gradacion

• Guia para obtener la mejor muestra biopsia• Guia para obtener la mejor muestra biopsia

• Estadificacion

•Monitoreo terapeutico

• Reestadificacion ( recurrencia local )

Respuesta Tumoral

1. Crecimiento enlentecido

2. Estasis

3. Necrosis ( coagulativa, licuefactiva)

4. Hemorragia

5. Seria acumulacion de fluidos5. Seria acumulacion de fluidos

6. Formacion de Tejido de Granulacion

7. Formacion de cicatriz

8. Perdida de vascularizacion

9. Perdida de elementos malignos

Definiendo Respuesta TumoralInterrogantes clinicos

1. Cuan temprano puedo detectar respuesta?

2. Cual es el mejor agente de tratamiento?

3. Es una imagen de la respuesta sustituto, o equivalente

de la efectividad del tratamiento?

4. PUEDE inferirse la evolucion del paciente?

5. Predice la imagen de la respuesta el curso posterior

del paciente , su evolucion?

Redefiniendo Respuesta Tumoral

Parametros Biologicos Tumorales Cuantificables por PETParametros Biologicos Tumorales Cuantificables por PET

• Osteosarcoma femoral

izquierdo tratado con

PET en SarcomasAplicaciones – monitoreo terapeutico

Basal Post-QTP

MIP

izquierdo tratado con

quimioterapia adyuvante

• Respuesta metabolica Respuesta metabolica

completacompleta

PET Transaxial

PET-CT

SUV = 7,8 SUV = 0,6

PRE QTPPRE QTP

SUV 7,4SUV 7,4

(corte hasta(corte hasta(corte hasta(corte hasta

2,5)2,5)

POST QTPPOST QTP

2 DOSIS2 DOSIS

SUV 0.9SUV 0.9

Sarcoma Ewing : Respuesta terapeutica evaluada por PET

April 2005, Volume 184, Number 4 - Pediatric Imaging

Pictorial Essay

PET/CT in the Evaluation of Childhood Sarcomas

M. Beth McCarville1 2, Ryan Christie2, Najat C. Daw3, Sheri L. Spunt3 and Sue C. Kaste

CONCLUSION. We found PET/CT useful in depicting an unknown primary

rhabdomyosarcoma and detecting unsuspected and unusual metastatic sites of childhood

sarcomas. It was useful in monitoring response to chemotherapy, radiation therapy, and

radiofrequency ablation and aided the postoperative evaluation of tumor resection sites

Fig. 6A. —16-year-

old boy with large

right pelvic Ewing's

Fig. 6B. —16-year-old boy

with large right pelvic right pelvic Ewing's

sarcoma, treated

preoperatively with

chemotherapy and

radiation therapy.

Maximum-intensity-

projection PET

image, obtained

before neoadjuvant

therapy, shows

intense FDG activity

in primary tumor

(arrow) without

evidence of

metastatic disease.

with large right pelvic

Ewing's sarcoma, treated

preoperatively with

chemotherapy and radiation

therapy. Maximum-intensity-

projection PET image,

obtained after neoadjuvant

therapy, shows minimal

activity within tumor (arrow),

suggestive of good

response. Pathologic Pathologic

inspection of resected inspection of resected

tumor showed less than tumor showed less than

5% residual viable tumor.5% residual viable tumor.

(a)

Figure 4: FDG-

PET/CT at

baseline, early

followup, and

after completion

of neoadjuvant

treatments in a

(b)

histopathological

responder (a)

and a

nonresponder

(b).

(a)

Figure 4: FDG-

PET/CT at

baseline, early

followup, and

after completion

of neoadjuvant

treatments in a

(b)

histopathological

responder (a)

and a

nonresponder

(b).

(a) ∆SUV Baseline-Followup (bars) and

SUVmax at Followup (numerical)

(b) ∆Size Baseline-Followup

Figure 3: (a) SUVmax values (numerical) and changes in SUVmax (bars) after completion of

neoadjuvant treatment for each patient. (b) depicts changes in tumor size from baseline to

end of treatment. Histopathologic responders are illustrated in orange. Three of four

histopathologic responders showed decreases in SUVmax by ≥60% from baseline to

followup scan. One histopathologic responder with a 38% decrease in FDG uptake from

baseline to followup showed an SUVmax value after completion of neoadjuvant therapy of

<2.5 and was therefore correctly classified. Size changes in response to treatment were

marginal.

IMAGEN FUNCIONAL CON PET en Sarcoma

Aplicaciones - Conclusiones

• Estadificacion y reestadificacion(Barrido de cuerpo entero util )

Auxilio valioso en evaluar posibles recurrencias locales

•Monitoreo terapeutico

ENORME valor clinico ENORME valor clinico

Cambios rapidamente evidenciables ( semanas)

Se requieren mas estudios para mejorar y estratificar la cuantificacion de la respuesta

Potenciales ventajas con trazadores alternativos ( FLT hipoxia, sintesis proteica, intervencion genetica, etc.)

IMAGEN FUNCIONAL CON PET en Sarcomas

Aplicaciones - Conclusiones

• Posible marcador grado benignidad vs . malignidad

provee informacion complementaria util

Debe considerarse en el contexto clinico (cuando!!)

Pareceria poder asumir valor pronostico independiente, Pareceria poder asumir valor pronostico independiente, necesitando mas estudios al respecto

• Utilidad conductora al seleccionar sitio a biopsiar

MUY valioso, particularmente PET/CT – extendido a intevenciones quirurgicas y/o radioterapeuticas

PositronEmissionTomographyP E TINSTRUMENTACION Y

METODOLOGIA

PET : Componentes

• Scanner – detector que exploraexplorael paciente y efectua reconstruccion tomograficareconstruccion tomografica

• Ciclotron - produce el emisor el emisor de positrones a detectarde positrones a detectarde positrones a detectarde positrones a detectarModulo de sintesis- produce el elemento ,compuesto o elemento ,compuesto o MOLECULA MOLECULA que se UNIRA por reaccion quimica al emisor de positrones y se incorporara al incorporara al proceso metabolico a explorarproceso metabolico a explorar

CPET

State of the Art Clinical Positron Emission Tomograph

Advanced detector technologyAdvanced detector technology

�� improved resolutionimproved resolution

Design features & benefitsDesign features & benefits

AMPLIA PROYECCION ASISTENCIAL DE UNA HERRAMIENTA DE INVESTIGACION

DIRECTA, CON EXPLORACIONES FUNCIONALES UNICAS Y NOTABLES

MEJORAS EN LA RESOLUCION ,CAPAZ DE CUANTIFICAR REALES MEDIDAS DE

CONCENTRACION DE LOS TRAZADORES CON UN FUTURO LIBRE DEL

CICLOTRON,PIONERO EN FUSION CON OTRAS TECNICAS TOMOGRAFICAS

A D A CADAC Laboratories

ADAC-PET Vers. 5.2 18

�� improved resolutionimproved resolution

(5 mm @ center)(5 mm @ center)

�� betterbetter homogeinityhomogeinity

�� larger diameterlarger diameter

(92 cm)(92 cm)

� Better image quality

fusión de imágenes(con TAC)Mapeo funcional Mapeo anatomico

Semicuantificacion Semicuantificacion

EXTREMA

SENSIBILIDAD

Proporcionamente

En algunas

situaciones

MENOR

ESPECIFICIDAD

Comienza a depender

Del operador

MENOR SENSIBILIDAD RELATIVA

•Anatomía

+ Función

•Eleva la especificidad

•Mejora localización especialmente en algunos

sitios como abdomen,pelvis o cuello

•Reduce en casos los resultados falsos +

•En otros es de poco valor , superflua.

Semicuantificacion

metabolica

Semicuantificacion

densitometrica

FUSION de PET + TAC = “ PIEDRA ROSETA “ para la “civilizacion anatomista “

Del operador

Mejora sobre todo ESPECIFICIDAD ,sin abandonar rol estadificador , mejorando la

comprension de localizacion de los hallazgos del PET , auxiliando especialmente algunas

Tacticas medicas desarrolladas sobre bases ANATOMICAS (Ej: Cirugia – Radioterapia)

PET

6

CTCTPET

PET /PET /

YA VIMOS LA MESA , LOS PLATOS , LOS

CUBIERTOS Y LA ETIQUETA A CUMPLIR

( TODOS VALIOSOS , COMPLEJOS Y

ELEGANTES ) PERO /..ELEGANTES ) PERO /..

¿¿¿ QUE HAY DE COMER $????¿¿¿ QUE HAY DE COMER $????

(EL MENU POSITRONICO)

SEGURIDAD RADIOLOGICA

JUSTIFICACION DE

LA PRACTICA

LIMITACION

DE LA

DOSIS

OPTIMIZACION DE LA

PROTECCION

POR QUE <.????

EL NUEVO PLATO PARECE MAS SALUDABLE

(a–c) Graphs show excess cancer incidence risks estimated to be associated with radiation from

a single whole-body 18F-FDG PET/CT examination at a given age.

Huang B et al. Radiology 2009;251:166-174

©2009 by Radiological Society of North America

(a–c) Graphs show excess cancer incidence risks estimated to be associated with radiation from a single whole-body 18F-FDG PET/CT examination at a given age.

(a–c) Graphs show excess cancer incidence risks estimated to be associated with radiation from a single whole-body 18F-FDG PET/CT examination at a given age.

Huang B et al. Radiology 2009;251:166-174

©2009 by Radiological Society of North America

Huang B et al. Radiology 2009;251:166-174

©2009 by Radiological Society of North America

PET : Imagen de Factores que

Limitan Respuesta a la Terapia

• Hipoxia– Efectos Directos: resistencia a

radiacion y quimioterapia

– Indirectos: Inestabilidad genetica

• VEGF, mutacion del p53

• Resistencia Multi Medicamentosa(MDR)

– via P-glicoproteina

– Requerimiento de Alta energia

$$$$$$$$$$$$$$$$$$$$$$

• Citrato de GALIO 67 3,3 mCi = 1176 $

• Cada mCi adicional = 351$

• FDG –f18 15 mCi = 1350$

• Cada mCi adicional = 98$• Cada mCi adicional = 98$

• Centellografia osea corporal = 1500$ +

material radiactivo = 680$ =2180 $

Factores en la Respuesta y la Resistencia

Receptores Receptores

de de

superficiesuperficie

OctreotidoOctreotido

Ritmo Ritmo

ProliferativoProliferativo

Timidina & Timidina &

AnalogosAnalogos

Ritmo Ritmo

GlicoliticoGlicolitico

FDGf18FDGf18

HipoxiaHipoxia

FMISO, EF1, FMISO, EF1, OctreotidoOctreotido

FMISO, EF1, FMISO, EF1,

ATSMATSM

Bombas de Bombas de

EflujoEflujo

MIBI, MIBI,

(Verapamilo, (Verapamilo,

Colchicina)Colchicina)

ReceptoresReceptores

NuclearesNucleares

FES, FDHTFES, FDHT

Clinical History

A 14-year-old girl was diagnosed with osteosarcoma of the lower end of the right femur. Chemotherapy was

recommended prior to surgery to amputate the right leg.

Imaging Findings

NUCLEAR MEDICINE PET/CT: January 2007

IMAGING FINDINGS: The initial PET/CT scan in January 2007 showed a hypermetabolic primary tumor with slight

lateral soft tissue extension but without skip lesions or metastases.

Treatment

The patient was started on chemotherapy with a follow-up PET/CT scan recommended for evaluation

before surgery was scheduled to amputate the right leg.

Follow-up Imaging Findings

NUCLEAR MEDICINE PET/CT: April 2007

IMAGING FINDINGS: The follow-up PET/CT scan performed in April 2007 after her initial

chemotherapy, showed gross decrease in uptake in the primary tumor, suggesting excellent response

to chemotherapy. The standard uptake value (SUV) decreased from 8.0 to 1.0.

• Treatment

Due to the PET/CT findings the surgical plan was altered and a local resection with limb salvage

was performed instead of amputation.

• Dr. Helen Nadel, BC Children's Hospital and BC Cancer Research Centre, Vancouver, Canada

RTA

QTP